{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T22:07:26Z","timestamp":1792534046824,"version":"4.5.0"},"reference-count":190,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nitric oxide (NO), a fundamental gaseous signaling molecule, is indispensable for cardiovascular homeostasis. This review synthesizes the expansive field of NO biology within the unifying framework of Nitric Oxide Equilibrium (NOE), i.e., the critical balance between its synthesis, bioavailability, and degradation. In a physiological state, NOE maintains vascular health by regulating blood pressure, preventing thrombosis, suppressing inflammation, and optimizing both cardiac and mitochondrial function. Here, we analyze how NOE disruption, primarily through oxidative stress and enzymatic dysfunction, underlies the pathogenesis of major cardiovascular diseases, including atherosclerosis, heart failure, ischemia\u2013reperfusion injury, and cerebrovascular diseases like stroke. A critical evaluation of therapeutic strategies designed to restore NOE is presented, encompassing classic NO donors and phosphodiesterase-5 inhibitors, alongside next-generation soluble guanylate cyclase modulators and precision nanomedicine approaches. By identifying key knowledge gaps and methodological hurdles, this review charts a course for future research focused on biomarker-guided interventions and personalized medicine. Ultimately, we frame the restoration of NOE as a paramount therapeutic goal, crucial to translating decades of molecular research into effective clinical practice.<\/jats:p>","DOI":"10.3390\/ijms27020629","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T11:11:21Z","timestamp":1767870681000},"page":"629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Nitric Oxide Signaling in Cardiovascular Physiology and Pathology: Mechanisms, Dysregulation, and Therapeutic Frontiers"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7517-2574","authenticated-orcid":false,"given":"Sakthipriyan","family":"Venkatesan","sequence":"first","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3338-5416","authenticated-orcid":false,"given":"Carlo","family":"Smirne","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4797-6161","authenticated-orcid":false,"given":"Carmen Imma","family":"Aquino","sequence":"additional","affiliation":[{"name":"Gynecology and Obstetrics Unit, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6801-0043","authenticated-orcid":false,"given":"Daniela","family":"Surico","sequence":"additional","affiliation":[{"name":"Gynecology and Obstetrics Unit, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5043-6676","authenticated-orcid":false,"given":"Valentino","family":"Remorgida","sequence":"additional","affiliation":[{"name":"Gynecology and Obstetrics Unit, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8810-4688","authenticated-orcid":false,"given":"Mohammad Mostafa","family":"Ola Pour","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9740-0155","authenticated-orcid":false,"given":"Mario","family":"Pirisi","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3012-259X","authenticated-orcid":false,"given":"Elena","family":"Grossini","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"ref_1","first-page":"303","article-title":"Nitric oxide in the cardiovascular system: A simple molecule with complex actions","volume":"20","author":"Strijdom","year":"2009","journal-title":"Cardiovasc. J. Afr."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kr\u00fcger-Genge, A., Blocki, A., Franke, R.P., and Jung, F. (2019). Vascular Endothelial Cell Biology: An Update. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184411"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1001\/jama.1996.03540140074032","article-title":"The 1996 Albert Lasker Medical Research Awards. The discovery of endothelium-derived relaxing factor and its importance in the identification of nitric oxide","volume":"276","author":"Furchgott","year":"1996","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1001\/jama.1996.03540140077033","article-title":"The 1996 Albert Lasker Medical Research Awards. Signal transduction using nitric oxide and cyclic guanosine monophosphate","volume":"276","author":"Murad","year":"1996","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9265","DOI":"10.1073\/pnas.84.24.9265","article-title":"Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide","volume":"84","author":"Ignarro","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1089\/ars.2009.2938","article-title":"Hydrogen sulfide: The third gasotransmitter in biology and medicine","volume":"12","author":"Wang","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"829d","DOI":"10.1093\/eurheartj\/ehr304","article-title":"Nitric oxide synthases: Regulation and function","volume":"33","author":"Sessa","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1253\/circj.CJ-09-0208","article-title":"Nitric oxide synthases and cardiovascular diseases: Insights from genetically modified mice","volume":"73","author":"Tsutsui","year":"2009","journal-title":"Circ. J."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Costa, E.D., Rezende, B.A., Cortes, S.F., and Lemos, V.S. (2016). Neuronal Nitric Oxide Synthase in Vascular Physiology and Diseases. Front. Physiol., 7.","DOI":"10.3389\/fphys.2016.00206"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1016\/j.cell.2022.06.010","article-title":"Nitric oxide signaling in health and disease","volume":"185","author":"Lundberg","year":"2022","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3892\/ijmm.2025.5593","article-title":"Nitric oxide mediated S-Nitrosylation contributes to signaling transduction in human physiological and pathological status","volume":"56","author":"Xu","year":"2025","journal-title":"Int. J. Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41392-024-02095-6","article-title":"Redox regulation: Mechanisms, biology and therapeutic targets in diseases","volume":"10","author":"Li","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e70133","DOI":"10.1002\/jbt.70133","article-title":"Oxidative\/Nitrosative Stress, Apoptosis, and Redox Signaling: Key Players in Neurodegenerative Diseases","volume":"39","year":"2025","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.freeradbiomed.2023.12.024","article-title":"Superoxide, nitric oxide and peroxynitrite production by macrophages under different physiological oxygen tensions","volume":"212","author":"Casella","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Belenichev, I., Popazova, O., Bukhtiyarova, N., Savchenko, D., Oksenych, V., and Kamyshnyi, O. (2024). Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection. Antioxidants, 13.","DOI":"10.3390\/antiox13050504"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1023\/A:1022199021949","article-title":"Nitric oxide, atherosclerosis and the clinical relevance of endothelial dysfunction","volume":"8","author":"Anderson","year":"2003","journal-title":"Heart Fail. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Caturano, A., Rocco, M., Tagliaferri, G., Piacevole, A., Nilo, D., Di Lorenzo, G., Iadicicco, I., Donnarumma, M., Galiero, R., and Acierno, C. (2025). Oxidative Stress and Cardiovascular Complications in Type 2 Diabetes: From Pathophysiology to Lifestyle Modifications. Antioxidants, 14.","DOI":"10.3390\/antiox14010072"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s11658-023-00423-2","article-title":"Endothelial dysfunction due to eNOS uncoupling: Molecular mechanisms as potential therapeutic targets","volume":"28","author":"Dobrucki","year":"2023","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1152\/physrev.00029.2006","article-title":"Nitric oxide and peroxynitrite in health and disease","volume":"87","author":"Pacher","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113073","DOI":"10.1016\/j.jinorgbio.2025.113073","article-title":"Restoring nitric oxide\/Peroxynitrite equilibrium in impaired human neural progenitor cells: Nanomedical approaches and their potential impact on neurodegenerative disease treatment","volume":"274","author":"Alsiraey","year":"2025","journal-title":"J. Inorg. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S56","DOI":"10.5830\/CVJA-2015-043","article-title":"Endothelial dysfunction: A unifying hypothesis for the burden of cardiovascular diseases in sub-Saharan Africa","volume":"26","author":"Sampson","year":"2015","journal-title":"Cardiovasc. J. Afr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/S0008-6363(03)00500-5","article-title":"The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor","volume":"59","year":"2003","journal-title":"Cardiovasc. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yang, Z., Du, C., Chang, Z., Yang, Y., and Hu, L. (2025). Role of oral and gut microbiomes in enterosalivary nitrate metabolism and their effects on systemic disease. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1612223"},{"key":"ref_24","first-page":"153","article-title":"Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: In Physiology and in Disease States","volume":"15","author":"Tran","year":"2022","journal-title":"Am. J. Biomed. Sci. Res."},{"key":"ref_25","first-page":"19","article-title":"Cardiovascular roles of nitric oxide: A review of insights from nitric oxide synthase gene disrupted mice","volume":"77","author":"Liu","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/nrcardio.2014.189","article-title":"Heart failure: Mitochondrial dysfunction and oxidative stress in CHF","volume":"12","author":"Okonko","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1161\/01.ATV.0000125114.88079.96","article-title":"Dysfunction of endothelial nitric oxide synthase and atherosclerosis","volume":"24","author":"Kawashima","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1093\/eurheartj\/ehu193","article-title":"Right heart dysfunction in heart failure with preserved ejection fraction","volume":"35","author":"Melenovsky","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.cardiores.2003.09.019","article-title":"Nitric oxide in myocardial ischemia\/reperfusion injury","volume":"61","author":"Schulz","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1111\/bph.14205","article-title":"PDE5 inhibitors\u2014Pharmacology and clinical applications 20 years after sildenafil discovery","volume":"175","author":"Andersson","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s11897-010-0045-1","article-title":"Soluble guanylate cyclase modulators in heart failure","volume":"8","author":"Mitrovic","year":"2011","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gonzalez, M., Clayton, S., Wauson, E., Christian, D., and Tran, Q.K. (2025). Promotion of nitric oxide production: Mechanisms, strategies, and possibilities. Front. Physiol., 16.","DOI":"10.3389\/fphys.2025.1545044"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"159","DOI":"10.52601\/bpr.2023.210045","article-title":"Insights into human eNOS, nNOS and iNOS structures and medicinal indications from statistical analyses of their interactions with bound compounds","volume":"9","author":"Dong","year":"2023","journal-title":"Biophys. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"30708","DOI":"10.1074\/jbc.M109.031682","article-title":"Regulation of interdomain interactions by calmodulin in inducible nitric-oxide synthase","volume":"284","author":"Xia","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mattila, J.T., and Thomas, A.C. (2014). Nitric oxide synthase: Non-canonical expression patterns. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00478"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1093\/emboj\/cdg078","article-title":"Structural basis for endothelial nitric oxide synthase binding to calmodulin","volume":"22","author":"Aoyagi","year":"2003","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16855","DOI":"10.1074\/jbc.M114.564005","article-title":"Architecture of the nitric-oxide synthase holoenzyme reveals large conformational changes and a calmodulin-driven release of the FMN domain","volume":"289","author":"Yokom","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_38","first-page":"10246","article-title":"Single crystal structural and absorption spectral characterizations of nitric oxide synthase complexed with N(omega)-hydroxy-L-arginine and diatomic ligands","volume":"47","author":"Doukov","year":"2008","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.jinorgbio.2011.06.003","article-title":"Binding kinetics of calmodulin with target peptides of three nitric oxide synthase isozymes","volume":"105","author":"Wu","year":"2011","journal-title":"J. Inorg. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.1111\/j.1742-4658.2011.08395.x","article-title":"Rate, affinity and calcium dependence of nitric oxide synthase isoform binding to the primary physiological regulator calmodulin","volume":"278","author":"McMurry","year":"2011","journal-title":"FEBS J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1046\/j.1365-201x.2000.00627.x","article-title":"Phosphorylation and activation of the endothelial nitric oxide synthase by fluid shear stress","volume":"168","author":"Fisslthaler","year":"2000","journal-title":"Acta Physiol. Scand."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105464","DOI":"10.1016\/j.jbc.2023.105464","article-title":"Mapping interactions of calmodulin and neuronal NO synthase by crosslinking and mass spectrometry","volume":"300","author":"Felker","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Salim, T., Sershen, C.L., and May, E.E. (2016). Investigating the Role of TNF-\u03b1 and IFN-\u03b3 Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153289"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"107781","DOI":"10.1016\/j.phrs.2025.107781","article-title":"Inducible nitric oxide synthase (iNOS): More than an inducible enzyme? Rethinking the classification of NOS isoforms","volume":"216","author":"Farahani","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1091\/mbc.E17-01-0049","article-title":"Reciprocal regulation of eNOS and caveolin-1 functions in endothelial cells","volume":"29","author":"Chen","year":"2018","journal-title":"Mol. Biol. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Troiano, J.A., Potje, S.R., Graton, M.E., Gon\u00e7alves, E.T., Tostes, R.C., and Antoniali, C. (2021). Caveolin-1\/Endothelial Nitric Oxide Synthase Interaction Is Reduced in Arteries From Pregnant Spontaneously Hypertensive Rats. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.760237"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/21224","article-title":"Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation","volume":"399","author":"Dimmeler","year":"1999","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chen, F., Kumar, S., Yu, Y., Aggarwal, S., Gross, C., Wang, Y., Chakraborty, T., Verin, A.D., Catravas, J.D., and Lucas, R. (2014). PKC-dependent phosphorylation of eNOS at T495 regulates eNOS coupling and endothelial barrier function in response to G+ -toxins. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099823"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bajec, T., and Poglajen, G. (2025). Targeting the NO-sGC-cGMP Pathway: Mechanisms of Action of Vericiguat in Chronic Heart Failure. Cells, 14.","DOI":"10.3390\/cells14171400"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1007\/s00204-025-04041-z","article-title":"The role of redox signaling in mitochondria and endoplasmic reticulum regulation in kidney diseases","volume":"99","year":"2025","journal-title":"Arch. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"C1424","DOI":"10.1152\/ajpcell.1996.271.5.C1424","article-title":"Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and ugly","volume":"271","author":"Beckman","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1021\/jp025518z","article-title":"The rate constant of the reaction of superoxide with nitrogen monoxide: Approaching the diffusion limit","volume":"106","author":"Nauser","year":"2002","journal-title":"J. Phys. Chem. A"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1021\/acs.chemrev.7b00568","article-title":"Biochemistry of Peroxynitrite and Protein Tyrosine Nitration","volume":"118","author":"Campolo","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5839","DOI":"10.1073\/pnas.1804932115","article-title":"Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine","volume":"115","author":"Radi","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Penna, C., and Pagliaro, P. (2025). Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases. Antioxidants, 14.","DOI":"10.3390\/antiox14030256"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9220","DOI":"10.1073\/pnas.95.16.9220","article-title":"Superoxide generation by endothelial nitric oxide synthase: The influence of cofactors","volume":"95","author":"Kalyanaraman","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.tcm.2004.10.003","article-title":"Tetrahydrobiopterin: Regulator of endothelial nitric oxide synthase in vascular disease","volume":"14","author":"Channon","year":"2004","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1006\/bbrc.1999.1422","article-title":"Oxidation of tetrahydrobiopterin by peroxynitrite: Implications for vascular dysfunction","volume":"263","author":"Milstien","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"22546","DOI":"10.1074\/jbc.M302227200","article-title":"Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: Implications for uncoupling endothelial nitric-oxide synthase","volume":"278","author":"Kuzkaya","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/S0008-6363(99)00162-5","article-title":"Biological significance of endogenous methylarginines that inhibit nitric oxide synthases","volume":"43","author":"Leiper","year":"1999","journal-title":"Cardiovasc. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1161\/01.STR.0000231640.32543.11","article-title":"ADMA increases arterial stiffness and decreases cerebral blood flow in humans","volume":"37","author":"Kielstein","year":"2006","journal-title":"Stroke"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10205","DOI":"10.1016\/S0021-9258(18)81786-0","article-title":"Purification and properties of a new enzyme, NG, NG-dimethylarginine dimethylaminohydrolase, from rat kidney","volume":"264","author":"Ogawa","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1161\/01.CIR.0000101924.04515.2E","article-title":"Dimethylarginine dimethylaminohydrolase regulates nitric oxide synthesis: Genetic and physiological evidence","volume":"108","author":"Dayoub","year":"2003","journal-title":"Circulation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S1567-5688(03)00033-3","article-title":"ADMA and oxidative stress","volume":"4","author":"Sydow","year":"2003","journal-title":"Atheroscler. Suppl."},{"key":"ref_65","first-page":"619207","article-title":"Regulation of DDAH1 as a Potential Therapeutic Target for Treating Cardiovascular Diseases","volume":"2013","author":"Liu","year":"2013","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"re2","DOI":"10.1126\/scisignal.268re2","article-title":"Signaling by gasotransmitters","volume":"2","author":"Mustafa","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e00710","DOI":"10.1016\/j.neurot.2025.e00710","article-title":"The role of gasotransmitters in Parkinson\u2019s disease: Interplay of nitric oxide, carbon monoxide, and hydrogen sulfide","volume":"22","author":"Fountos","year":"2025","journal-title":"Neurotherapeutics"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2489612","DOI":"10.1080\/20002297.2025.2489612","article-title":"Nitrate reduction by salivary bacteria, glucose metabolism, and lifestyle","volume":"17","author":"Guo","year":"2025","journal-title":"J. Oral Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.freeradbiomed.2016.12.015","article-title":"Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health","volume":"105","author":"Koch","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1002\/1873-3468.14859","article-title":"Do oral and gut microbiota communicate through redox pathways? A novel asset of the nitrate-nitrite-NO pathway","volume":"598","author":"Paiva","year":"2024","journal-title":"FEBS Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1007\/s40279-014-0149-y","article-title":"Dietary nitrate supplementation and exercise performance","volume":"44","author":"Jones","year":"2014","journal-title":"Sports Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e35987","DOI":"10.7554\/eLife.35987","article-title":"Antibiotic-induced changes in the microbiota disrupt redox dynamics in the gut","volume":"7","author":"Reese","year":"2018","journal-title":"eLife"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1161\/HYPERTENSIONAHA.107.103523","article-title":"Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite","volume":"51","author":"Webb","year":"2008","journal-title":"Hypertension"},{"key":"ref_74","first-page":"4727","article-title":"Quantitative aspects of nitric oxide production from nitrate and nitrite","volume":"22","author":"Ghasemi","year":"2023","journal-title":"EXCLI J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"17855","DOI":"10.1074\/jbc.M801785200","article-title":"Nitric oxide production from nitrite occurs primarily in tissues not in the blood: Critical role of xanthine oxidase and aldehyde oxidase","volume":"283","author":"Li","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Chai, X., Liu, L., and Chen, F. (2024). Oral nitrate-reducing bacteria as potential probiotics for blood pressure homeostasis. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1337281"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1186\/s40001-023-01413-y","article-title":"From nitrate to NO: Potential effects of nitrate-reducing bacteria on systemic health and disease","volume":"28","author":"Liu","year":"2023","journal-title":"Eur. J. Med. Res."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"He, J., Zhang, P., Shen, L., Niu, L., Tan, Y., Chen, L., Zhao, Y., Bai, L., Hao, X., and Li, X. (2020). Short-Chain Fatty Acids and Their Association with Signaling Pathways in Inflammation, Glucose and Lipid Metabolism. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176356"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1039\/c2cs15271a","article-title":"Nitric oxide release: Part III. Measurement and reporting","volume":"41","author":"Coneski","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4333","DOI":"10.1093\/jxb\/erz242","article-title":"Current approaches to measure nitric oxide in plants","volume":"70","author":"Vishwakarma","year":"2019","journal-title":"J. Exp. Bot."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1089\/ars.2017.7403","article-title":"Protein S-Nitrosylation: Determinants of Specificity and Enzymatic Regulation of S-Nitrosothiol-Based Signaling","volume":"30","author":"Stomberski","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"7420","DOI":"10.1073\/pnas.0600729103","article-title":"Identification of S-nitrosylation motifs by site-specific mapping of the S-nitrosocysteine proteome in human vascular smooth muscle cells","volume":"103","author":"Greco","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1073\/pnas.98.1.355","article-title":"The biological lifetime of nitric oxide: Implications for transport and signaling","volume":"98","author":"Thomas","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1089\/ars.2007.1959","article-title":"Nitric oxide in the vasculature: Where does it come from and where does it go? A quantitative perspective","volume":"10","author":"Chen","year":"2008","journal-title":"Antioxid. Redox Signal."},{"key":"ref_85","first-page":"555","article-title":"Calcium oscillations and endothelial nitric oxide synthase activity: A mathematical model","volume":"116","author":"Carrizzo","year":"2014","journal-title":"J. Appl. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/nrd2222","article-title":"Peroxynitrite: Biochemistry, pathophysiology and development of therapeutics","volume":"6","author":"Ischiropoulos","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41392-023-01430-7","article-title":"Signaling pathways in vascular function and hypertension: Molecular mechanisms and therapeutic interventions","volume":"8","author":"Ma","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1089\/ars.2023.0406","article-title":"Roles of Protein S-Nitrosylation in Endothelial Homeostasis and Dysfunction","volume":"40","author":"Luo","year":"2024","journal-title":"Antioxid. Redox Signal."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1111\/jth.15844","article-title":"The NO\/cGMP\/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders","volume":"20","author":"Degjoni","year":"2022","journal-title":"J. Thromb. Haemost."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/jth.13910","article-title":"Negative regulators of platelet activation and adhesion","volume":"16","author":"Stefanini","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Aguilar, G., Koning, T., Ehrenfeld, P., and S\u00e1nchez, F.A. (2020). Role of NO and S-nitrosylation in the Expression of Endothelial Adhesion Proteins That Regulate Leukocyte and Tumor Cell Adhesion. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.595526"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.yjmcc.2008.07.015","article-title":"Nitric oxide signaling and the regulation of myocardial function","volume":"45","author":"Ziolo","year":"2008","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/jcp.20929","article-title":"The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a protein kinase G\/MAPK pathway","volume":"211","author":"Pyriochou","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4229","DOI":"10.7150\/thno.84049","article-title":"iNOS aggravates pressure overload-induced cardiac dysfunction via activation of the cytosolic-mtDNA-mediated cGAS-STING pathway","volume":"13","author":"Guo","year":"2023","journal-title":"Theranostics"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1152\/physrev.00042.2007","article-title":"Nitric Oxide and Cardiac Function","volume":"89","author":"Balligand","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.cardiores.2007.03.022","article-title":"Nitric oxide and mitochondrial respiration in the heart","volume":"75","author":"Brown","year":"2002","journal-title":"Cardiovasc. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/S0005-2728(00)00238-3","article-title":"Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase","volume":"1504","author":"Brown","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1073\/pnas.0506562103","article-title":"Nitric oxide inhibition of respiration involves both competitive (heme) and noncompetitive (copper) binding to cytochrome c oxidase","volume":"103","author":"Mason","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1126\/science.1079368","article-title":"Mitochondrial biogenesis in mammals: The role of endogenous nitric oxide","volume":"299","author":"Nisoli","year":"2003","journal-title":"Science"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1101\/gad.1177604","article-title":"Transcriptional regulatory circuits controlling mitochondrial biogenesis and function","volume":"18","author":"Kelly","year":"2004","journal-title":"Genes Dev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"783","DOI":"10.2165\/00007256-200333110-00001","article-title":"Regulation of mitochondrial biogenesis in muscle by endurance exercise","volume":"33","author":"Irrcher","year":"2003","journal-title":"Sports Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/nrm3013","article-title":"Mitochondrial fusion and fission in cell life and death","volume":"11","author":"Westermann","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/s41419-018-0910-5","article-title":"PDI-mediated S-nitrosylation of DRP1 facilitates DRP1-S616 phosphorylation and mitochondrial fission in CA1 neurons","volume":"9","author":"Lee","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.mito.2010.04.007","article-title":"S-nitrosylation of Drp1 links excessive mitochondrial fission to neuronal injury in neurodegeneration","volume":"10","author":"Nakamura","year":"2010","journal-title":"Mitochondrion"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1038\/cdd.2010.48","article-title":"Nitric oxide inhibition of Drp1-mediated mitochondrial fission is critical for myogenic differentiation","volume":"17","author":"Falcone","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_106","first-page":"H1600","article-title":"Impaired wound healing and angiogenesis in eNOS-deficient mice","volume":"277","author":"Lee","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Huang, H., and Huang, W. (2022). Regulation of Endothelial Progenitor Cell Functions in Ischemic Heart Disease: New Therapeutic Targets for Cardiac Remodeling and Repair. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.896782"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0092-8674(02)00754-7","article-title":"Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand","volume":"109","author":"Heissig","year":"2002","journal-title":"Cell"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/j.1365-2125.2009.03486.x","article-title":"Progenitors in motion: Mechanisms of mobilization of endothelial progenitor cells","volume":"68","author":"Tilling","year":"2009","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"oeac078","DOI":"10.1093\/ehjopen\/oeac078","article-title":"Endothelial progenitor cell mobilization based on exercise volume in patients with cardiovascular disease and healthy individuals: A systematic review and meta-analysis","volume":"2","author":"Mitsiou","year":"2022","journal-title":"Eur. Heart J. Open"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/j.1751-7176.2012.00606.x","article-title":"Impaired vasodilation in the pathogenesis of hypertension: Focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins","volume":"14","author":"Giles","year":"2012","journal-title":"J. Clin. Hypertens."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Boughaleb, H., Lobysheva, I., Dei Zotti, F., Balligand, J.L., and Montiel, V. (2022). Biological Assessment of the NO-Dependent Endothelial Function. Molecules, 27.","DOI":"10.3390\/molecules27227921"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1161\/01.RES.87.10.840","article-title":"Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress","volume":"87","author":"Cai","year":"2000","journal-title":"Circ. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.mce.2008.11.003","article-title":"NADPH oxidases and angiotensin II receptor signaling","volume":"302","author":"Garrido","year":"2009","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e117","DOI":"10.1161\/ATVBAHA.121.317239","article-title":"NADPH Oxidase 1 Mediates Acute Blood Pressure Response to Angiotensin II by Contributing to Calcium Influx in Vascular Smooth Muscle Cells","volume":"42","author":"Park","year":"2022","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1007\/s11897-012-0097-5","article-title":"Recoupling the cardiac nitric oxide synthases: Tetrahydrobiopterin synthesis and recycling","volume":"9","author":"Alkaitis","year":"2012","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"de Queiroz, T.M., Monteiro, M.M., and Braga, V.A. (2013). Angiotensin-II-derived reactive oxygen species on baroreflex sensitivity during hypertension: New perspectives. Front. Physiol., 4.","DOI":"10.3389\/fphys.2013.00105"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.tem.2009.03.005","article-title":"eNOS, metabolic syndrome and cardiovascular disease","volume":"20","author":"Huang","year":"2009","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.ecl.2008.06.001","article-title":"An integrated view of insulin resistance and endothelial dysfunction","volume":"37","author":"Muniyappa","year":"2008","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.2337\/db08-0961","article-title":"Increased MAPK activation and impaired insulin signaling in subcutaneous microvascular endothelial cells in type 2 diabetes: The role of endothelin-1","volume":"58","author":"Gogg","year":"2009","journal-title":"Diabetes"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"E685","DOI":"10.1152\/ajpendo.2001.280.5.E685","article-title":"Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE","volume":"280","author":"Wautier","year":"2001","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"16005","DOI":"10.1038\/s41598-020-72943-2","article-title":"Asymmetric dimethylarginine (ADMA) accelerates renal cell fibrosis under high glucose condition through NOX4\/ROS\/ERK signaling pathway","volume":"10","author":"Jayachandran","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"0252","DOI":"10.34133\/bmr.0252","article-title":"Endothelial Dysfunction in Atherosclerosis: Experimental Models and Therapeutics","volume":"29","author":"Kopych","year":"2025","journal-title":"Biomater. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e651","DOI":"10.1002\/mco2.651","article-title":"Endothelial dysfunction: Molecular mechanisms and clinical implications","volume":"5","author":"Wang","year":"2024","journal-title":"MedComm"},{"key":"ref_125","first-page":"201","article-title":"A protective role for nitric oxide in the oxidative modification of low density lipoproteins","volume":"315","author":"Yates","year":"1992","journal-title":"FEBS Lett."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Ijaz, A., Yarlagadda, B., and Orecchioni, M. (2025). Foamy macrophages in atherosclerosis: Unraveling the balance between pro- and anti-inflammatory roles in disease progression. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1589629"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s11883-025-01294-y","article-title":"The Atherosclerotic Plaque Microenvironment as a Therapeutic Target","volume":"27","author":"Pandit","year":"2025","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.pathophys.2006.05.002","article-title":"Oxidative stress and atherosclerosis","volume":"13","author":"Singh","year":"2006","journal-title":"Pathophysiology"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1038\/nm1459","article-title":"Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis","volume":"12","author":"Clarke","year":"2006","journal-title":"Nat. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41569-019-0326-7","article-title":"Neutrophils as regulators of cardiovascular inflammation","volume":"17","author":"Braster","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.carpath.2011.11.007","article-title":"The pathophysiology of heart failure","volume":"21","author":"Kemp","year":"2012","journal-title":"Cardiovasc. Pathol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1161\/HYPERTENSIONAHA.124.21709","article-title":"Cardiac cGMP Regulation and Therapeutic Applications","volume":"82","author":"Mishra","year":"2025","journal-title":"Hypertension"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Yuan, Y., Tian, Y., Jiang, H., Cai, L.Y., Song, J., Peng, R., and Zhang, X.M. (2023). Mechanism of PGC-1\u03b1-mediated mitochondrial biogenesis in cerebral ischemia-reperfusion injury. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1224964"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Badoer, E. (2022). New Insights Into the Role of Inflammation in the Brain in Heart Failure. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.837723"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1161\/CIRCRESAHA.124.326042","article-title":"Dysregulated Protein s-Nitrosylation Promotes Nitrosative Stress and Disease Progression in Heart Failure With Preserved Ejection Fraction","volume":"137","author":"Li","year":"2025","journal-title":"Circ. Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1042\/BJ20120787","article-title":"Nitric oxide signalling pathway in Duchenne muscular dystrophy mice: Up-regulation of L-arginine transporters","volume":"449","author":"Ramachandran","year":"2013","journal-title":"Biochem. J."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Alsadder, L., and Hamadah, A. (2025). Cardiac Ischaemia-Reperfusion Injury: Pathophysiology, Therapeutic Targets and Future Interventions. Biomedicines, 13.","DOI":"10.3390\/biomedicines13092084"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1023\/A:1020718619155","article-title":"Nitric oxide and cardioprotection during ischemia-reperfusion","volume":"7","author":"Jugdutt","year":"2002","journal-title":"Heart Fail. Rev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"23439","DOI":"10.1038\/s41598-025-07070-x","article-title":"Mechanisms of delayed ischemia\/reperfusion evoked ROS generation in the hippocampal CA1 zone of adult mouse brain slices","volume":"15","author":"Medvedeva","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1755-1536-6-11","article-title":"Neutrophil roles in left ventricular remodeling following myocardial infarction","volume":"6","author":"Ma","year":"2013","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Meng, X., Zheng, Z., Yang, L., Yang, C., Li, X., and Hao, Y. (2025). Dynamic mechanisms and targeted interventions in cerebral ischemia-reperfusion injury: Pathological cascade from ischemia to reperfusion and promising therapeutic strategies. Front. Neurosci., 19.","DOI":"10.3389\/fnins.2025.1649533"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Pang, Q., Meng, X., Zhou, Z., You, L., Yuan, J., Feng, Q., and Zhu, B. (2025). Temporal regulation of genetic programs governing multiple cell death during myocardial ischemia-reperfusion injury. Front. Genet., 16.","DOI":"10.3389\/fgene.2025.1632867"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neuron.2017.07.030","article-title":"The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease","volume":"96","author":"Iadecola","year":"2017","journal-title":"Neuron"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Yang, M., Liu, B., Chen, B., Shen, Y., and Liu, G. (2025). Cerebral ischemia-reperfusion injury: Mechanisms and promising therapies. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1613464"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1161\/01.STR.0000028343.25901.09","article-title":"Neuroprotection by selective nitric oxide synthase inhibition at 24 hours after perinatal hypoxia-ischemia","volume":"33","author":"Koster","year":"2002","journal-title":"Stroke"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1748-1716.2010.02229.x","article-title":"NAD+ depletion or PAR polymer formation: Which plays the role of executioner in ischaemic cell death?","volume":"203","author":"Siegel","year":"2011","journal-title":"Acta Physiol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.nbd.2008.08.005","article-title":"Blood-Brain Barrier Tight Junction Permeability and Ischemic Stroke","volume":"32","author":"Sandoval","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"C343","DOI":"10.1152\/ajpcell.00095.2018","article-title":"Blood-brain barrier dysfunction in ischemic stroke: Targeting tight junctions and transporters for vascular protection","volume":"315","author":"Abdullahi","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"8306","DOI":"10.1073\/pnas.122225199","article-title":"Identification of the enzymatic mechanism of nitroglycerin bioactivation","volume":"99","author":"Chen","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"25i","DOI":"10.1016\/j.amjcard.2005.07.030","article-title":"The oxidative stress concept of nitrate tolerance and the antioxidant properties of hydralazine","volume":"96","author":"Daiber","year":"2005","journal-title":"Am. J. Cardiol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1161\/01.ATV.0000179599.71086.89","article-title":"Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans","volume":"25","author":"Mackenzie","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.niox.2016.01.006","article-title":"Dinitrosyl iron complexes with thiol-containing ligands as a \u201cworking model\u201d of endogenous nitric oxide carriers","volume":"54","author":"Vanin","year":"2016","journal-title":"Nitric Oxide"},{"key":"ref_153","first-page":"9753820","article-title":"Dinitrosyl Iron Complexes: A New Class of Hypotensive Drugs","volume":"2022","author":"Chazov","year":"2022","journal-title":"Cardiovasc. Ther."},{"key":"ref_154","first-page":"13668","article-title":"Nitrosyl iron complexes\u2014Synthesis, structure and biological activity","volume":"50","author":"Lewandowska","year":"2021","journal-title":"Dalton Trans."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"35","DOI":"10.15420\/ecr.2017:22:2","article-title":"Treatment Selection in Pulmonary Arterial Hypertension: Phosphodiesterase Type 5 Inhibitors versus Soluble Guanylate Cyclase Stimulator","volume":"13","author":"Watanabe","year":"2018","journal-title":"Eur. Cardiol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"5492","DOI":"10.1038\/s41467-021-25617-0","article-title":"Activation mechanism of human soluble guanylate cyclase by stimulators and activators","volume":"12","author":"Liu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s40272-020-00384-5","article-title":"Therapeutic Potential of Citrulline as an Arginine Supplement: A Clinical Pharmacology Review","volume":"22","author":"Rashid","year":"2020","journal-title":"Paediatr. Drugs"},{"key":"ref_158","first-page":"55","article-title":"L-Arginine therapy in cardiovascular pathologies: Beneficial or dangerous?","volume":"11","year":"2008","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Tsuboi, T., Maeda, M., and Hayashi, T. (2018). Administration of L-arginine plus L-citrulline or L-citrulline alone successfully retarded endothelial senescence. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192252"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"103447","DOI":"10.1016\/j.redox.2024.103447","article-title":"Tetrahydrobiopterin as a rheostat of cell resistance to oxidant injury","volume":"79","author":"Traeger","year":"2025","journal-title":"Redox Biol."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Miao, S.H., Gao, S.Q., Li, H.X., Zhuang, Y.S., Wang, X., Li, T., Gao, C.C., Han, Y.L., Qiu, J.-Y., and Zhou, M.-L. (2023). Increased NOX2 expression in astrocytes leads to eNOS uncoupling through dihydrofolate reductase in endothelial cells after subarachnoid hemorrhage. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1121944"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1007\/s11883-011-0209-9","article-title":"Dietary nitrates, nitrites, and cardiovascular disease","volume":"13","author":"Hord","year":"2011","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1161\/HYPERTENSIONAHA.111.00933","article-title":"Enhanced vasodilator activity of nitrite in hypertension: Critical role for erythrocytic xanthine oxidoreductase and translational potential","volume":"61","author":"Ghosh","year":"2013","journal-title":"Hypertension"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.2174\/138161210794519246","article-title":"The biology and therapeutic potential of the DDAH\/ADMA pathway","volume":"16","author":"Arrigoni","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Hulin, J.A., Gubareva, E.A., Jarzebska, N., Rodionov, R.N., Mangoni, A.A., and Tommasi, S. (2020). Inhibition of Dimethylarginine Dimethylaminohydrolase (DDAH) Enzymes as an Emerging Therapeutic Strategy to Target Angiogenesis and Vasculogenic Mimicry in Cancer. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.01455"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12951-018-0392-8","article-title":"Nano based drug delivery systems: Recent developments and future prospects","volume":"16","author":"Patra","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1701043","DOI":"10.1002\/advs.201701043","article-title":"Progress and Promise of Nitric Oxide-Releasing Platforms","volume":"5","author":"Yang","year":"2018","journal-title":"Adv. Sci."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0355-7","article-title":"Mitochondrial dysfunction and oxidative stress in heart disease","volume":"51","author":"Peoples","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1097\/00005373-199712000-00006","article-title":"Inhaled nitric oxide in acute respiratory distress syndrome","volume":"43","author":"Johannigman","year":"1997","journal-title":"J. Trauma"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"e003598","DOI":"10.1161\/CIRCGEN.121.003598","article-title":"Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease","volume":"15","author":"Khera","year":"2022","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1093\/eurheartj\/ehq340","article-title":"Assessment of atherosclerosis: The role of flow-mediated dilatation","volume":"31","author":"Charakida","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.freeradbiomed.2005.08.025","article-title":"Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans","volume":"40","author":"Kleinbongard","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1074\/jbc.272.5.2841","article-title":"A novel reaction mechanism for the formation of S-nitrosothiol in vivo","volume":"272","author":"Gow","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/tpj.2009.38","article-title":"eNOS haplotypes affect the responsiveness to antihypertensive therapy in preeclampsia but not in gestational hypertension","volume":"10","author":"Sandrim","year":"2010","journal-title":"Pharmacogenomics J."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coph.2017.02.002","article-title":"Influence of sex on cardiovascular drug responses: Role of estrogen","volume":"33","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1001\/jama.295.1.58","article-title":"L-arginine therapy in acute myocardial infarction: The Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial","volume":"295","author":"Schulman","year":"2006","journal-title":"JAMA"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"25804","DOI":"10.1074\/jbc.273.40.25804","article-title":"Superoxide generation from endothelial nitric-oxide synthase. A Ca2+\/calmodulin-dependent and tetrahydrobiopterin regulatory process","volume":"273","author":"Xia","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"3579","DOI":"10.2174\/13816128113196660748","article-title":"eNOS uncoupling in cardiovascular diseases--the role of oxidative stress and inflammation","volume":"20","author":"Karbach","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"w20125","DOI":"10.4414\/smw.2019.20125","article-title":"Biomarkers in cardiovascular medicine: Towards precision medicine","volume":"149","author":"Gualandro","year":"2019","journal-title":"Swiss Med. Wkly."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1016\/j.amjcard.2017.06.012","article-title":"The Nitric Oxide Pathway in Pulmonary Vascular Disease","volume":"120","author":"Klinger","year":"2017","journal-title":"Am. J. Cardiol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1161\/CIRCULATIONAHA.105.539437","article-title":"nNOS gene deletion exacerbates pathological left ventricular remodeling and functional deterioration after myocardial infarction","volume":"112","author":"Dawson","year":"2005","journal-title":"Circulation"},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Puente, E., and Palomero, J. (2021). Genetically Encoded Biosensors to Monitor Intracellular Reactive Oxygen and Nitrogen Species and Glutathione Redox Potential in Skeletal Muscle Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910876"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"14785","DOI":"10.1021\/acs.est.0c04709","article-title":"Future Adoption of Direct Measurement Techniques for Regulatory Measurements of Nitrogen Dioxide: Drivers and Challenges","volume":"54","author":"Worton","year":"2020","journal-title":"Environ. Sci. Technol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1161\/01.CIR.102.22.2707","article-title":"In vivo and in vitro evidence for impaired arginine transport in human heart failure","volume":"102","author":"Kaye","year":"2000","journal-title":"Circulation"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Antoniou, M., Jorgensen, A.L., and Kolamunnage-Dona, R. (2016). Biomarker-Guided Adaptive Trial Designs in Phase II and Phase III: A Methodological Review. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149803"},{"key":"ref_186","first-page":"519","article-title":"Nitric Oxide and Cardiovascular Regulation","volume":"70","author":"Fadel","year":"2017","journal-title":"Hypertension"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"e002200","DOI":"10.1136\/openhrt-2022-002200","article-title":"Coronary endothelial dysfunction: From pathogenesis to clinical implications","volume":"9","author":"Bockus","year":"2022","journal-title":"Open Heart"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.freeradbiomed.2008.03.020","article-title":"The chemical biology of nitric oxide: Implications in cellular signaling","volume":"45","author":"Thomas","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1161\/CIRCRESAHA.115.306301","article-title":"Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis","volume":"118","author":"Gimbrone","year":"2016","journal-title":"Circ. Res."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Villiers, C.B., Plans-Beriso, E., Erady, C., Blackburn, L., Wilson, H., Turner, H., Kuhn, I., Barahona-L\u00f3pez, C., Diez-Echave, P., and Hern\u00e1ndez, O.R. (2025). Biomarkers for Personalised Primary or Secondary Prevention in Cardiovascular Diseases: A Rapid Scoping Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199346"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/629\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T05:27:26Z","timestamp":1768022846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":190,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020629"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020629","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]}}}