{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:47:18Z","timestamp":1791996438396,"version":"4.4.0"},"reference-count":152,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["2018\/29\/B\/NZ4\/00771"],"award-info":[{"award-number":["2018\/29\/B\/NZ4\/00771"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["2019\/33\/B\/NZ4\/01760"],"award-info":[{"award-number":["2019\/33\/B\/NZ4\/01760"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["2021\/43\/B\/NZ4\/00339"],"award-info":[{"award-number":["2021\/43\/B\/NZ4\/00339"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["17GRNT32910002"],"award-info":[{"award-number":["17GRNT32910002"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Heart Association","award":["2018\/29\/B\/NZ4\/00771"],"award-info":[{"award-number":["2018\/29\/B\/NZ4\/00771"]}]},{"name":"American Heart Association","award":["2019\/33\/B\/NZ4\/01760"],"award-info":[{"award-number":["2019\/33\/B\/NZ4\/01760"]}]},{"name":"American Heart Association","award":["2021\/43\/B\/NZ4\/00339"],"award-info":[{"award-number":["2021\/43\/B\/NZ4\/00339"]}]},{"name":"American Heart Association","award":["17GRNT32910002"],"award-info":[{"award-number":["17GRNT32910002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atherosclerosis is accompanied by inflammation that underlies cardiovascular disease (CVD) and its vascular manifestations, including acute stroke, myocardial infarction, and peripheral artery disease, the leading causes of morbidity\/mortality worldwide. The monolayer of endothelial cells formed on the luminal surface of arteries and veins regulates vascular tone and permeability, which supports vascular homeostasis. Endothelial dysfunction, the first step in the development of atherosclerosis, is caused by mechanical and biochemical factors that disrupt vascular homeostasis and induce inflammation. Together with increased plasma levels of low-density lipoprotein (LDL), diabetes, hypertension, cigarette smoking, infectious microorganisms, and genetic factors, epidemiological studies established that dysregulated metabolism of homocysteine (Hcy) causing hyperhomocysteinemia (HHcy) is associated with CVD. Patients with severe HHcy exhibit severe CVD and die prematurely due to vascular complications. Biochemically, HHcy is characterized by elevated levels of Hcy and related metabolites such as Hcy-thiolactone and N-Hcy-protein, seen in genetic and nutritional deficiencies in Hcy metabolism in humans and animals. The only known source of Hcy in humans is methionine released in the gut from dietary protein. Hcy is generated from S-adenosylhomocysteine (AdoHcy) and metabolized to cystathionine by cystathionine \u03b2-synthase (CBS) and to Hcy-thiolactone by methionyl-tRNA synthetase. Hcy-thiolactone, a chemically reactive thioester, modifies protein lysine residues, generating N-homocysteinylated (N-Hcy)-protein. N-Hcy-proteins lose their normal native function and become cytotoxic, autoimmunogenic, proinflammatory, prothrombotic, and proatherogenic. Accumulating evidence, discussed in this review, shows that these Hcy metabolites can promote endothelial dysfunction, CVD, and stroke in humans by inducing pro-atherogenic changes in gene expression, upregulating mTOR signaling, and inhibiting autophagy through epigenetic mechanisms involving specific microRNAs, histone demethylase PHF8, and methylated histone H4K20me1. Clinical studies, also discussed in this review, show that cystathionine and Hcy-thiolactone are associated with myocardial infarction and ischemic stroke by influencing blood clotting. These findings contribute to our understanding of the complex mechanisms underlying endothelial dysfunction, atherosclerosis, CVD, and stroke and identify potential targets for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/ijms26020746","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T12:27:54Z","timestamp":1737030474000},"page":"746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Homocysteine Metabolites, Endothelial Dysfunction, and Cardiovascular Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5845-4409","authenticated-orcid":false,"given":"Hieronim","family":"Jakubowski","sequence":"first","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, International Center for Public Health, New Jersey Medical School, Rutgers University, Newark, NJ 07103, USA"},{"name":"Department of Biochemistry and Biotechnology, Pozna\u0144 University of Life Sciences, 60-632 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3908-7735","authenticated-orcid":false,"given":"\u0141ukasz","family":"Witucki","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Pozna\u0144 University of Life Sciences, 60-632 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1002\/hcs2.116","article-title":"Improving Transitional Care after Acute Myocardial Infarction: A Scoping Review","volume":"3","author":"Homem","year":"2024","journal-title":"Health Care Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3509","DOI":"10.4103\/jfmpc.jfmpc_1874_23","article-title":"Distinctive characteristics, risk factors, and prevention of premature myocardial infarction: A narrative review","volume":"13","author":"Rallidis","year":"2024","journal-title":"J. Family Med. Prim. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102629","DOI":"10.1016\/j.arr.2024.102629","article-title":"Regulated Cell Death in Acute Myocardial Infarction: Molecular Mechanisms and Therapeutic Implications","volume":"104","author":"Zhu","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"oeae087","DOI":"10.1093\/ehjopen\/oeae087","article-title":"Call to Action for Acute Myocardial Infarction in Women: International Multi-Disciplinary Practical Roadmap","volume":"4","author":"Hawranek","year":"2024","journal-title":"Eur. Heart J. Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.neuroscience.2024.12.024","article-title":"Unravelling Neuroregenerative and Neuroprotective Roles of Wnt\/\u03b2-Catenin Pathway in Ischemic Stroke: Insights into Molecular Mechanisms","volume":"565","author":"Yadava","year":"2025","journal-title":"Neuroscience"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mai, L.M., Joundi, R.A., Katsanos, A.H., Selim, M., and Shoamanesh, A. (2024). Pathophysiology of Intracerebral Hemorrhage: Recovery Trajectories. Stroke.","DOI":"10.1161\/STROKEAHA.124.046130"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102638","DOI":"10.1016\/j.arr.2024.102638","article-title":"Glial Polarization in Neurological Diseases: Molecular Mechanisms and Therapeutic Opportunities","volume":"104","author":"Liu","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s40035-024-00457-2","article-title":"Cellular Senescence as a Key Contributor to Secondary Neurodegeneration in Traumatic Brain Injury and Stroke","volume":"13","author":"Huang","year":"2024","journal-title":"Transl. Neurodegener."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"123305","DOI":"10.1016\/j.lfs.2024.123305","article-title":"The Mechanism of Acetylation-Mediated Fusion of Lysosomes with Autophagosomes in Neurons after Ischemic Stroke","volume":"362","author":"Yu","year":"2024","journal-title":"Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"qyae123","DOI":"10.1093\/ehjimp\/qyae123","article-title":"Guidelines at a Crossroad: Comparing European and American Guidelines Regarding the Use of Imaging in Peripheral Vascular Arterial Disease and Aortic Disease","volume":"2","author":"Liga","year":"2024","journal-title":"Eur. Heart J. Imaging Methods Pract."},{"key":"ref_11","first-page":"420","article-title":"Shockwave for Peripheral Artery Disease: An Update on Trial Data","volume":"65","author":"Pacor","year":"2024","journal-title":"J. Cardiovasc. Surg."},{"key":"ref_12","first-page":"541","article-title":"Management of Arterial Hypertension in Patients with Peripheral Arterial Disease","volume":"43","author":"Mikhailidis","year":"2024","journal-title":"Int. Angiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e031446","DOI":"10.1161\/JAHA.123.031446","article-title":"Racial and Socioeconomic Health Disparities in Peripheral Artery Disease","volume":"13","author":"Thomas","year":"2024","journal-title":"J. Am. Heart Assoc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e347","DOI":"10.1161\/CIR.0000000000001209","article-title":"2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association","volume":"149","author":"Martin","year":"2024","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nature01323","article-title":"Inflammation in Atherosclerosis","volume":"420","author":"Libby","year":"2002","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis\u2014An Inflammatory Disease","volume":"340","author":"Ross","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.carpath.2013.12.004","article-title":"Anitschkow and the Lipid Hypothesis of Atherosclerosis","volume":"23","author":"Buja","year":"2014","journal-title":"Cardiovasc. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1152\/physrev.00047.2003","article-title":"Role of Oxidative Modifications in Atherosclerosis","volume":"84","author":"Stocker","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1097\/MCA.0000000000000187","article-title":"Antioxidants and Coronary Artery Disease: From Pathophysiology to Preventive Therapy","volume":"26","author":"Leopold","year":"2015","journal-title":"Coron. Artery Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev.med.60.041807.123308","article-title":"The Treatment of Hyperhomocysteinemia","volume":"60","author":"Maron","year":"2009","journal-title":"Annu. Rev. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Esse, R., Barroso, M., Tavares de Almeida, I., and Castro, R. (2019). The Contribution of Homocysteine Metabolism Disruption to Endothelial Dysfunction: State-of-the-Art. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040867"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1111\/joim.13279","article-title":"Homocysteine\u2014From Disease Biomarker to Disease Prevention","volume":"290","author":"Smith","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/0735-1097(93)90203-D","article-title":"Impaired Endothelial Function Occurs in the Systemic Arteries of Children with Homozygous Homocystinuria but Not in Their Heterozygous Parents","volume":"22","author":"Celermajer","year":"1993","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1161\/01.CIR.95.5.1119","article-title":"Hyperhomocyst(e)Inemia Is Associated with Impaired Endothelium-Dependent Vasodilation in Humans","volume":"95","author":"Tawakol","year":"1997","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1161\/01.CIR.96.8.2542","article-title":"Hyperhomocyst(e)Inemia Is a Risk Factor for Arterial Endothelial Dysfunction in Humans","volume":"96","author":"Woo","year":"1997","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1111\/andr.13169","article-title":"Homocysteine Levels Correlate with Velocimetric Parameters in Patients with Erectile Dysfunction Undergoing Penile Duplex Ultrasound","volume":"10","author":"Salvio","year":"2022","journal-title":"Andrology"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Salvio, G., Ciarloni, A., Cutini, M., and Balercia, G. (2021). Hyperhomocysteinemia: Focus on Endothelial Damage as a Cause of Erectile Dysfunction. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010418"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ymgme.2011.04.012","article-title":"Constitutive Induction of Pro-Inflammatory and Chemotactic Cytokines in Cystathionine Beta-Synthase Deficient Homocystinuria","volume":"103","author":"Keating","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sikora, M., Lewandowska, I., Marczak, \u0141., Bretes, E., and Jakubowski, H. (2020). Cystathionine \u03b2-Synthase Deficiency: Different Changes in Proteomes of Thrombosis-Resistant Cbs-\/- Mice and Thrombosis-Prone CBS-\/- Humans. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-67672-5"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sikora, M., Lewandowska, I., Kupc, M., Kubalska, J., Graban, A., Marczak, \u0141., Ka\u017amierski, R., and Jakubowski, H. (2019). Serum Proteome Alterations in Human Cystathionine \u03b2-Synthase Deficiency and Ischemic Stroke Subtypes. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123096"},{"key":"ref_31","first-page":"1","article-title":"The Natural History of Homocystinuria Due to Cystathionine Beta-Synthase Deficiency","volume":"37","author":"Mudd","year":"1985","journal-title":"Am. J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1021\/acs.biomac.7b00154","article-title":"Engineering and Characterization of an Enzyme Replacement Therapy for Classical Homocystinuria","volume":"18","author":"Majtan","year":"2017","journal-title":"Biomacromolecules"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1023\/B:BOLI.0000009963.88420.c2","article-title":"Homocystinuria Due to Cystathionine Beta-Synthase Deficiency: Novel Biochemical Findings and Treatment Efficacy","volume":"26","author":"Zeman","year":"2003","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Utyro, O., Per\u0142a-Kaj\u00e1n, J., and Jakubowski, H. (2020). The Cbs Locus Affects the Expression of Senescence Markers and mtDNA Copy Number, but Not Telomere Dynamics in Mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072520"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1111\/j.1538-7836.2005.01364.x","article-title":"Mechanisms of Homocysteine-Induced Atherothrombosis","volume":"3","author":"Lentz","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1161\/ATVBAHA.108.166421","article-title":"Murine Models of Hyperhomocysteinemia and Their Vascular Phenotypes","volume":"28","author":"Dayal","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1161\/01.CIR.103.22.2717","article-title":"Homocysteine Induces Expression and Secretion of Monocyte Chemoattractant Protein-1 and Interleukin-8 in Human Aortic Endothelial Cells: Implications for Vascular Disease","volume":"103","author":"Poddar","year":"2001","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11010-006-9204-9","article-title":"Comparative Study on in Vitro Effects of Homocysteine Thiolactone and Homocysteine on HUVEC Cells: Evidence for a Stronger Proapoptotic and Proinflammative Homocysteine Thiolactone","volume":"291","author":"Kerkeni","year":"2006","journal-title":"Mol. Cell. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1172\/JCI116187","article-title":"Adverse Vascular Effects of Homocysteine Are Modulated by Endothelium-Derived Relaxing Factor and Related Oxides of Nitrogen","volume":"91","author":"Stamler","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.3892\/ijmm.2014.1920","article-title":"Homocysteine Reduces Protein S-Nitrosylation in Endothelium","volume":"34","author":"Chen","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"H2344","DOI":"10.1152\/ajpheart.00432.2007","article-title":"Homocysteine Induces VCAM-1 Gene Expression through NF-kappaB and NAD(P)H Oxidase Activation: Protective Role of Mediterranean Diet Polyphenolic Antioxidants","volume":"293","author":"Carluccio","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1056\/NEJMoa060900","article-title":"Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease","volume":"354","author":"Lonn","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1161\/01.STR.0000185929.38534.f3","article-title":"Vitamin Intervention for Stroke Prevention Trial: An Efficacy Analysis","volume":"36","author":"Spence","year":"2005","journal-title":"Stroke"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1161\/STROKEAHA.108.529503","article-title":"Homocysteine-lowering therapy and stroke risk, severity, and disability: Additional findings from the HOPE 2 trial","volume":"40","author":"Saposnik","year":"2009","journal-title":"Stroke"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1001\/jama.300.7.795","article-title":"Mortality and Cardiovascular Events in Patients Treated with Homocysteine-Lowering B Vitamins After Coronary Angiography: A Randomized Controlled Trial","volume":"300","author":"Ebbing","year":"2008","journal-title":"JAMA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1365-2796.2010.02259.x","article-title":"Combined Analyses and Extended Follow-up of Two Randomized Controlled Homocysteine-Lowering B-Vitamin Trials","volume":"268","author":"Ebbing","year":"2010","journal-title":"J. Intern. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1056\/NEJMoa055227","article-title":"Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction","volume":"354","author":"Ueland","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wald, D.S., Morris, J.K., and Wald, N.J. (2011). Reconciling the Evidence on Serum Homocysteine and Ischaemic Heart Disease: A Meta-Analysis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016473"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nrneurol.2012.77","article-title":"Anticoagulant Therapy for Patients with Ischaemic Stroke","volume":"8","author":"Hankey","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/S1474-4422(12)70091-1","article-title":"Antiplatelet Therapy and the Effects of B Vitamins in Patients with Previous Stroke or Transient Ischaemic Attack: A Post-Hoc Subanalysis of VITATOPS, a Randomised, Placebo-Controlled Trial","volume":"11","author":"Hankey","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1177\/1747493015616512","article-title":"Effect of B-Vitamins on Stroke Risk among Individuals with Vascular Disease Who Are Not on Antiplatelets: A Meta-Analysis","volume":"11","author":"Park","year":"2016","journal-title":"Int. J. Stroke"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1161\/STROKEAHA.114.006927","article-title":"Differential Effect of B-Vitamin Therapy by Antiplatelet Use on Risk of Recurrent Vascular Events after Stroke","volume":"46","author":"Arshi","year":"2015","journal-title":"Stroke"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jimd.12009","article-title":"Vitamin B12, Folate, and the Methionine Remethylation Cycle-Biochemistry, Pathways, and Regulation","volume":"42","author":"Froese","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1515\/cclm-2012-0689","article-title":"Betaine Homocysteine Methyltransferase (BHMT)-Dependent Remethylation Pathway in Human Healthy and Tumoral Liver","volume":"51","author":"Pellanda","year":"2013","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lan, X., Field, M.S., and Stover, P.J. (2018). Cell Cycle Regulation of Folate-Mediated One-Carbon Metabolism. Wiley Interdiscip. Rev. Syst. Biol. Med., 10.","DOI":"10.1002\/wsbm.1426"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Rom\u00e1n, G.C., Mancera-P\u00e1ez, O., and Bernal, C. (2019). Epigenetic Factors in Late-Onset Alzheimer\u2019s Disease: MTHFR and CTH Gene Polymorphisms, Metabolic Transsulfuration and Methylation Pathways, and B Vitamins. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020319"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1515\/revneuro-2023-0039","article-title":"Transsulfuration Pathway: A Targeting Neuromodulator in Parkinson\u2019s Disease","volume":"34","author":"Gonsebatt","year":"2023","journal-title":"Rev. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e14158","DOI":"10.1111\/eci.14158","article-title":"Transsulfuration and Folate Pathways in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis","volume":"54","author":"Mangoni","year":"2024","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1152\/physrev.00003.2018","article-title":"Homocysteine Modification in Protein Structure\/Function and Human Disease","volume":"99","author":"Jakubowski","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Jakubowski, H. (2024). Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer\u2019s Disease. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202406.0219.v1"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1161\/01.ATV.20.7.1704","article-title":"Homocysteine and Its Disulfide Derivatives: A Suggested Consensus Terminology","volume":"20","author":"Mudd","year":"2000","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1373\/clinchem.2004.042531","article-title":"Urinary Excretion of Homocysteine-Thiolactone in Humans","volume":"51","author":"Chwatko","year":"2005","journal-title":"Clin. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1096\/fj.06-7435com","article-title":"Mutations in Methylenetetrahydrofolate Reductase or Cystathionine Beta-Synthase Gene, or a High-Methionine Diet, Increase Homocysteine Thiolactone Levels in Humans and Mice","volume":"21","author":"Chwatko","year":"2007","journal-title":"FASEB J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1096\/fj.08-127548","article-title":"Genetic or Nutritional Disorders in Homocysteine or Folate Metabolism Increase Protein N-Homocysteinylation in Mice","volume":"23","author":"Jakubowski","year":"2009","journal-title":"FASEB J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4071","DOI":"10.1096\/fj.08-112086","article-title":"Mutations in Cystathionine \u03b2-Synthase or Methylenetetrahydrofolate Reductase Gene Increase N-Homocysteinylated Protein Levels in Humans","volume":"22","author":"Jakubowski","year":"2008","journal-title":"FASEB J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e008824","DOI":"10.1161\/JAHA.118.008824","article-title":"Plasma Cystathionine and Risk of Incident Stroke in Patients with Suspected Stable Angina Pectoris","volume":"7","author":"Dhar","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ijcard.2018.04.083","article-title":"Plasma Cystathionine and Risk of Acute Myocardial Infarction among Patients with Coronary Heart Disease: Results from Two Independent Cohorts","volume":"266","author":"Dhar","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.1182\/blood.V81.12.3404.3404","article-title":"Elevation of Serum Cystathionine Levels in Patients with Cobalamin and Folate Deficiency","volume":"81","author":"Stabler","year":"1993","journal-title":"Blood"},{"key":"ref_69","first-page":"149","article-title":"Metabolic Profiling of Total Homocysteine and Related Compounds in Hyperhomocysteinemia: Utility and Limitations in Diagnosing the Cause of Puzzling Thrombophilia in a Family","volume":"11","author":"Stabler","year":"2013","journal-title":"JIMD Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1096\/fj.08-120584","article-title":"Mouse Models of Cystathionine Beta-Synthase Deficiency Reveal Significant Threshold Effects of Hyperhomocysteinemia","volume":"23","author":"Gupta","year":"2009","journal-title":"FASEB J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1093\/ajcn\/86.6.1581","article-title":"S-Adenosylhomocysteine: A Better Indicator of Vascular Disease than Homocysteine?","volume":"86","author":"Wagner","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1093\/ajcn\/nqy391","article-title":"Elevated Plasma Cystathionine Is Associated with Increased Risk of Mortality among Patients with Suspected or Established Coronary Heart Disease","volume":"109","author":"Dhar","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/joim.12834","article-title":"Urinary Excretion of Homocysteine Thiolactone and the Risk of Acute Myocardial Infarction in Coronary Artery Disease Patients: The WENBIT Trial","volume":"285","author":"Borowczyk","year":"2019","journal-title":"J. Intern. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1161\/01.STR.0000128412.59768.6e","article-title":"Autoantibodies against N-Homocysteinylated Proteins in Humans: Implications for Atherosclerosis","volume":"35","author":"Undas","year":"2004","journal-title":"Stroke"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1160\/TH04-08-0493","article-title":"Antibodies to N-Homocysteinylated Albumin as a Marker for Early-Onset Coronary Artery Disease in Men","volume":"93","author":"Undas","year":"2005","journal-title":"Thromb. Haemost."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1160\/TH06-04-0228","article-title":"Folic Acid Administration and Antibodies against Homocysteinylated Proteins in Subjects with Hyperhomocysteinemia","volume":"96","author":"Undas","year":"2006","journal-title":"Thromb. Haemost."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0021-9258(18)70253-6","article-title":"The Enzymatic Synthesis of S-Adenosyl-L-Homocysteine from Adenosine and Homocysteine","volume":"234","author":"Cantoni","year":"1959","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Kusakabe, Y., Ishihara, M., Umeda, T., Kuroda, D., Nakanishi, M., Kitade, Y., Gouda, H., Nakamura, K.T., and Tanaka, N. (2015). Structural Insights into the Reaction Mechanism of S-Adenosyl-L-Homocysteine Hydrolase. Sci. Rep., 5.","DOI":"10.1038\/srep16641"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1107\/S0907444911055090","article-title":"High-Resolution Structures of Complexes of Plant S-Adenosyl-L-Homocysteine Hydrolase (Lupinus Luteus)","volume":"68","author":"Brzezinski","year":"2012","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1007\/s00726-015-1956-7","article-title":"Homocysteine Thiolactone and N-Homocysteinylated Protein Induce pro-Atherogenic Changes in Gene Expression in Human Vascular Endothelial Cells","volume":"47","author":"Gurda","year":"2015","journal-title":"Amino Acids"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/0003-9861(74)90306-3","article-title":"Methionine Metabolism in Mammals: Regulatory Effects of S-Adenosylhomocysteine","volume":"165","author":"Finkelstein","year":"1974","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1093\/ndt\/13.3.656","article-title":"Evidence for Disturbed S-Adenosylmethionine: S-Adenosylhomocysteine Ratio in Patients with End-Stage Renal Failure: A Cause for Disturbed Methylation Reactions?","volume":"13","author":"Loehrer","year":"1998","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1093\/ajcn\/74.6.723","article-title":"Plasma S-Adenosylhomocysteine Is a More Sensitive Indicator of Cardiovascular Disease than Plasma Homocysteine","volume":"74","author":"Kerins","year":"2001","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.metabol.2005.08.025","article-title":"Relationship between Plasma S-Adenosylhomocysteine Concentration and Glomerular Filtration Rate in Children","volume":"55","author":"Jabs","year":"2006","journal-title":"Metabolism"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1046\/j.1523-1755.1998.00983.x","article-title":"No Net Renal Extraction of Homocysteine in Fasting Humans","volume":"54","author":"Donker","year":"1998","journal-title":"Kidney Int."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1046\/j.1365-2362.2003.01104.x","article-title":"S-Adenosylhomocysteine and the Ratio of S-Adenosylmethionine to S-Adenosylhomocysteine Are Not Related to Folate, Cobalamin and Vitamin B6 Concentrations","volume":"33","author":"Becker","year":"2003","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cca.2008.05.018","article-title":"Elevated Serum Levels of S-Adenosylhomocysteine, but Not Homocysteine, Are Associated with Cardiovascular Disease in Stage 5 Chronic Kidney Disease Patients","volume":"395","author":"Valli","year":"2008","journal-title":"Clin. Chim. Acta"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.cca.2017.07.001","article-title":"The Relationship between S-Adenosylhomocysteine and Coronary Artery Lesions: A Case Control Study","volume":"471","author":"Huang","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.3945\/ajcn.113.058727","article-title":"Plasma S-Adenosylhomocysteine Is Associated with the Risk of Cardiovascular Events in Patients Undergoing Coronary Angiography: A Cohort Study","volume":"98","author":"Xiao","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1161\/CIRCULATIONAHA.118.036336","article-title":"Inhibition of S-Adenosylhomocysteine Hydrolase Induces Endothelial Dysfunction via Epigenetic Regulation of P66shc-Mediated Oxidative Stress Pathway","volume":"139","author":"Xiao","year":"2019","journal-title":"Circulation"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1017\/S0007114509993552","article-title":"Homocysteine-Lowering Vitamins Do Not Lower Plasma S-Adenosylhomocysteine in Older People with Elevated Homocysteine Concentrations","volume":"103","author":"Green","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1054\/clnu.2001.0523","article-title":"Methionine-Loading Test: Evaluation of Adverse Effects and Safety in an Epidemiological Study","volume":"21","author":"Andel","year":"2002","journal-title":"Clin. Nutr."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1056\/NEJM199104253241701","article-title":"Hyperhomocysteinemia: An Independent Risk Factor for Vascular Disease","volume":"324","author":"Clarke","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1161\/01.ATV.19.12.2922","article-title":"Physiological Increments in Plasma Homocysteine Induce Vascular Endothelial Dysfunction in Normal Human Subjects","volume":"19","author":"Chambers","year":"1999","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1161\/hh1401.093459","article-title":"Investigation of Relationship between Reduced, Oxidized, and Protein-Bound Homocysteine and Vascular Endothelial Function in Healthy Human Subjects","volume":"89","author":"Chambers","year":"2001","journal-title":"Circ. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1161\/01.RES.87.1.45","article-title":"Homocysteine Thiolactone and Protein Homocysteinylation in Human Endothelial Cells: Implications for Atherosclerosis","volume":"87","author":"Jakubowski","year":"2000","journal-title":"Circ. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ab.2016.06.002","article-title":"Quantification of Urinary S- and N-Homocysteinylated Protein and Homocysteine-Thiolactone in Mice","volume":"508","author":"Jakubowski","year":"2016","journal-title":"Anal. Biochem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3233\/JAD-2012-111940","article-title":"Metabolism and Neurotoxicity of Homocysteine Thiolactone in Mice: Evidence for a Protective Role of Paraoxonase 1","volume":"30","author":"Borowczyk","year":"2012","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s00726-011-1207-5","article-title":"Metabolism and Neurotoxicity of Homocysteine Thiolactone in Mice: Protective Role of Bleomycin Hydrolase","volume":"43","author":"Borowczyk","year":"2012","journal-title":"Amino. Acids"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/0887-2333(93)90076-H","article-title":"Stereospecific in Vitro Embryotoxicity of L-Homocysteine in Pre- and Post-Implantation Rodent Embryos","volume":"7","author":"Klaasboer","year":"1993","journal-title":"Toxicol. In Vitro"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"30425","DOI":"10.1074\/jbc.C200267200","article-title":"Homocysteine Is a Protein Amino Acid in Humans: IMPLICATIONS FOR HOMOCYSTEINE-LINKED DISEASE","volume":"277","author":"Jakubowski","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1373\/clinchem.2006.074302","article-title":"Bound Homocysteine, Cysteine, and Cysteinylglycine Distribution between Albumin and Globulins","volume":"52","author":"Hortin","year":"2006","journal-title":"Clin. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1021\/bi052076j","article-title":"Modification of Fibrinogen by Homocysteine Thiolactone Increases Resistance to Fibrinolysis: A Potential Mechanism of the Thrombotic Tendency in Hyperhomocysteinemia","volume":"45","author":"Sauls","year":"2006","journal-title":"Biochemistry"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.jmb.2010.05.039","article-title":"Protein N-Homocysteinylation Induces the Formation of Toxic Amyloid-like Protofibrils","volume":"400","author":"Paoli","year":"2010","journal-title":"J. Mol. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00726-013-1617-7","article-title":"Identification of N-Homocysteinylation Sites in Plasma Proteins","volume":"46","author":"Sikora","year":"2014","journal-title":"Amino Acids"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1002\/jimd.12661","article-title":"Homocysteine Metabolites Inhibit Autophagy, Elevate Amyloid Beta, and Induce Neuropathy by Impairing Phf8\/H4K20me1-Dependent Epigenetic Regulation of mTOR in Cystathionine \u03b2-Synthase-Deficient Mice","volume":"46","author":"Witucki","year":"2023","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.celrep.2018.09.022","article-title":"Colonic Lysine Homocysteinylation Induced by High-Fat Diet Suppresses DNA Damage Repair: Cell Reports","volume":"25","author":"Wang","year":"2018","journal-title":"Cell Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.trecan.2018.10.006","article-title":"Protein N-Homocysteinylation and Colorectal Cancer","volume":"5","author":"Jakubowski","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1161\/01.ATV.11.3.663","article-title":"Homocysteine Thiolactone Disposal by Human Arterial Endothelial Cells and Serum in Vitro","volume":"11","author":"Dudman","year":"1991","journal-title":"Arterioscler. Thromb."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S0076-6879(83)91043-1","article-title":"Manual Micro-Sequence Analysis of Polypeptides Using Dimethylaminoazobenzene Isothiocyanate","volume":"91","author":"Chang","year":"1983","journal-title":"Methods Enzymol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"8039","DOI":"10.1002\/chem.200600785","article-title":"Mechanism of the Condensation of Homocysteine Thiolactone with Aldehydes","volume":"12","author":"Jakubowski","year":"2006","journal-title":"Chem. Eur. J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3957","DOI":"10.1074\/jbc.275.6.3957","article-title":"Calcium-Dependent Human Serum Homocysteine Thiolactone Hydrolase. A Protective Mechanism against Protein N-Homocysteinylation","volume":"275","author":"Jakubowski","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1007\/s00018-003-3204-7","article-title":"Molecular Basis of Homocysteine Toxicity in Humans","volume":"61","author":"Jakubowski","year":"2004","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1016\/S0021-9258(19)67504-6","article-title":"Metabolism of Homocysteine Thiolactone in Human Cell Cultures. Possible Mechanism for Pathological Consequences of Elevated Homocysteine Levels","volume":"272","author":"Jakubowski","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.bbagrm.2015.11.005","article-title":"Sequence-Non-Specific Effects Generated by Various Types of RNA Interference Triggers","volume":"1859","author":"Olejniczak","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Minjares, M., Wu, W., and Wang, J.-M. (2023). Oxidative Stress and MicroRNAs in Endothelial Cells under Metabolic Disorders. Cells, 12.","DOI":"10.3390\/cells12091341"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/aps.2018.30","article-title":"miRNAS in Cardiovascular Diseases: Potential Biomarkers, Therapeutic Targets and Challenges","volume":"39","author":"Zhou","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1161\/STROKEAHA.120.031543","article-title":"Circulatory MicroRNAs as Potential Biomarkers for Stroke Risk: The Rotterdam Study","volume":"52","author":"Mens","year":"2021","journal-title":"Stroke"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41467-017-02531-y","article-title":"Phf8 Histone Demethylase Deficiency Causes Cognitive Impairments through the mTOR Pathway","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1136\/jmg.2004.029439","article-title":"Mutations in PHF8 Are Associated with X Linked Mental Retardation and Cleft Lip\/Cleft Palate","volume":"42","author":"Laumonnier","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_121","first-page":"100102","article-title":"Variants in PHF8 Cause a Spectrum of X-Linked Neurodevelopmental Disorders and Facial Dysmorphology","volume":"3","author":"Sobering","year":"2022","journal-title":"HGG Adv."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1533033820967472","DOI":"10.1177\/1533033820967472","article-title":"MYC Regulates PHF8, Which Promotes the Progression of Gastric Cancer by Suppressing miR-22-3p","volume":"19","author":"Cai","year":"2020","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.cell.2013.03.043","article-title":"Mapping the Human miRNA Interactome by CLASH Reveals Frequent Noncanonical Binding","volume":"153","author":"Helwak","year":"2013","journal-title":"Cell"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Witucki, \u0141., and Jakubowski, H. (2023). Depletion of Paraoxonase 1 (Pon1) Dysregulates mTOR, Autophagy, and Accelerates Amyloid Beta Accumulation in Mice. Cells, 12.","DOI":"10.3390\/cells12050746"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Kaldirim, M., Lang, A., Pfeiler, S., Fiegenbaum, P., Kelm, M., B\u00f6nner, F., and Gerdes, N. (2022). Modulation of mTOR Signaling in Cardiovascular Disease to Target Acute and Chronic Inflammation. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.907348"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"41902","DOI":"10.1155\/2018\/6141902","article-title":"Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases","volume":"2018","author":"Samidurai","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e9469","DOI":"10.15252\/emmm.201809469","article-title":"Inhibiting MARSs Reduces Hyperhomocysteinemia-Associated Neural Tube and Congenital Heart Defects","volume":"12","author":"Mei","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"e70072","DOI":"10.1096\/fj.202302116R","article-title":"Homocysteine Metabolites Impair the PHF8\/H4K20me1\/mTOR\/Autophagy Pathway by Upregulating the Expression of Histone Demethylase PHF8-Targeting microRNAs in Human Vascular Endothelial Cells and Mice","volume":"38","author":"Witucki","year":"2024","journal-title":"FASEB J."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"6019","DOI":"10.1096\/fj.201800346R","article-title":"Paraoxonase 1 Q192R Genotype and Activity Affect Homocysteine Thiolactone Levels in Humans","volume":"32","author":"Borowczyk","year":"2018","journal-title":"FASEB J."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.atherosclerosis.2015.12.021","article-title":"Serum Paraoxonase-1 Activity and Risk of Incident Cardiovascular Disease: The PREVEND Study and Meta-Analysis of Prospective Population Studies","volume":"245","author":"Kunutsor","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.jjcc.2016.08.013","article-title":"Prognostic Impact of Homocysteine Levels and Homocysteine Thiolactonase Activity on Long-Term Clinical Outcomes in Patients Undergoing Percutaneous Coronary Intervention","volume":"69","author":"Hassan","year":"2017","journal-title":"J. Cardiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e88","DOI":"10.1161\/ATVBAHA.111.230631","article-title":"Fibrin Clot Structure and Function: A Role in the Pathophysiology of Arterial and Venous Thromboembolic Diseases","volume":"31","author":"Undas","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1161\/ATVBAHA.107.153221","article-title":"EuroCLOT Investigators Heritability of Clot Formation, Morphology, and Lysis: The EuroCLOT Study","volume":"27","author":"Carter","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Sikora, M., Skrzydlewski, P., Per\u0142a-Kaj\u00e1n, J., and Jakubowski, H. (2022). Homocysteine Thiolactone Contributes to the Prognostic Value of Fibrin Clot Structure\/Function in Coronary Artery Disease. PLoS ONE, 17.","DOI":"10.1101\/2022.07.12.22277430"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1007\/s12325-008-0097-8","article-title":"Plasma Homocysteine Thiolactone Associated with Risk of Macrovasculopathy in Chinese Patients with Type 2 Diabetes Mellitus","volume":"25","author":"Gu","year":"2008","journal-title":"Adv. Ther."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.2337\/dc10-0132","article-title":"Homocysteinethiolactone and Paraoxonase","volume":"33","author":"Barathi","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Sikora, M., Bretes, E., Per\u0142a-Kaj\u00e1n, J., Utyro, O., Borowczyk, K., Piechocka, J., G\u0142owacki, R., Wojtasz, I., Ka\u017amierski, R., and Jakubowski, H. (2024). Homocysteine Thiolactone and Other Sulfur-Containing Amino Acid Metabolites Are Associated with Fibrin Clot Properties and the Risk of Ischemic Stroke. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-60706-2"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1373\/clinchem.2003.026252","article-title":"Quantification of Serum and Urinary S-Adenosylmethionine and S-Adenosylhomocysteine by Stable-Isotope-Dilution Liquid Chromatography-Mass Spectrometry","volume":"50","author":"Stabler","year":"2004","journal-title":"Clin. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0022-3476(65)80121-4","article-title":"Homocystinuria: Clinical and Pathological Review of Ten Cases","volume":"66","author":"Carson","year":"1965","journal-title":"J. Pediatr."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1096\/fasebj.13.15.2277","article-title":"Protein Homocysteinylation: Possible Mechanism Underlying Pathological Consequences of Elevated Homocysteine Levels","volume":"13","author":"Jakubowski","year":"1999","journal-title":"FASEB J."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Jakubowski, H. (2013). Homocysteine in Protein Structure\/Function and Human Disease: Chemical Biology of Homocysteine-Containing Proteins, Springer.","DOI":"10.1007\/978-3-7091-1410-0"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"10864","DOI":"10.1074\/jbc.M313268200","article-title":"Cross-Talk between Cys34 and Lysine Residues in Human Serum Albumin Revealed by N-Homocysteinylation","volume":"279","author":"Glowacki","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ab.2010.04.034","article-title":"Direct Monitoring of Albumin Lysine-525 N-Homocysteinylation in Human Serum by Liquid Chromatography\/Mass Spectrometry","volume":"405","author":"Sikora","year":"2010","journal-title":"Anal. Biochem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.jprot.2011.01.021","article-title":"Analysis of Site-Specific N-Homocysteinylation of Human Serum Albumin in Vitro and in Vivo Using MALDI-ToF and LC-MS\/MS Mass Spectrometry","volume":"74","author":"Marczak","year":"2011","journal-title":"J. Proteomics"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Sikora, M., Marczak, \u0141., Per\u0142a-Kajan, J., and Jakubowski, H. (2019). Sex Affects N-Homocysteinylation at Lysine Residue 212 of Albumin in Mice. Scientific Reports. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-38784-4"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ymgme.2010.06.007","article-title":"Cystathionine Beta-Synthase Null Homocystinuric Mice Fail to Exhibit Altered Hemostasis or Lowering of Plasma Homocysteine in Response to Betaine Treatment","volume":"101","author":"Maclean","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"377S","DOI":"10.1093\/jn\/130.2.377S","article-title":"Homocysteine Thiolactone: Metabolic Origin and Protein Homocysteinylation in Humans","volume":"130","author":"Jakubowski","year":"2000","journal-title":"J. Nutr."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1007\/s11239-014-1063-8","article-title":"Impact of Homocysteine-Thiolactone on Plasma Fibrin Networks","volume":"38","author":"Genoud","year":"2014","journal-title":"J. Thromb. Thrombolysis."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1093\/cvr\/cvad017","article-title":"Fibrin Clot Properties in Cardiovascular Disease: From Basic Mechanisms to Clinical Practice","volume":"119","author":"Undas","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0049-3848(96)00111-9","article-title":"Fibrinogen and Fibrin--Proteins with Complex Roles in Hemostasis and Thrombosis","volume":"83","year":"1996","journal-title":"Thromb. Res."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Nakashima, F., Shibata, T., Kamiya, K., Yoshitake, J., Kikuchi, R., Matsushita, T., Ishii, I., Gim\u00e9nez-Bastida, J.A., Schneider, C., and Uchida, K. (2018). Structural and Functional Insights into S-Thiolation of Human Serum Albumins. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-19610-9"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1097\/00001721-199412000-00002","article-title":"Coagulation Factors and Markers of Activation of Coagulation in Homocystinuria (HOCY): A Study in Two Siblings","volume":"5","author":"Schienle","year":"1994","journal-title":"Blood Coagul. Fibrinolysis"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/746\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:30:16Z","timestamp":1759919416000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,16]]},"references-count":152,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26020746"],"URL":"https:\/\/doi.org\/10.3390\/ijms26020746","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,16]]}}}