{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:58:50Z","timestamp":1790697530007,"version":"4.1.0"},"reference-count":123,"publisher":"IMR Press","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82300311"],"award-info":[{"award-number":["82300311"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82570561"],"award-info":[{"award-number":["82570561"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82200499"],"award-info":[{"award-number":["82200499"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82270346"],"award-info":[{"award-number":["82270346"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82241212"],"award-info":[{"award-number":["82241212"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82170334"],"award-info":[{"award-number":["82170334"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82300312"],"award-info":[{"award-number":["82300312"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Natural Science Foundation of Jiangsu Province of China","award":["BK20241720"],"award-info":[{"award-number":["BK20241720"]}]},{"name":"Key Project supported by Medical Science and technology development Foundation, Nanjing Department of Health","award":["JQX24002"],"award-info":[{"award-number":["JQX24002"]}]},{"name":"Jiangsu Association for Science &amp; Technology Youth Science &amp; Technology Talents Lifting Project","award":["JSTJ-2024-382"],"award-info":[{"award-number":["JSTJ-2024-382"]}],"id":[{"id":"https:\/\/ror.org\/019t77f77","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Nanjing Municipal Healthcare Science and Technology Development Special Funds","award":["YKK24107"],"award-info":[{"award-number":["YKK24107"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Cardiovasc. Med."],"abstract":"<jats:p>Endothelial cells regulate hemodynamics, inflammation, and vascular barrier integrity, thereby playing a central role in vascular homeostasis. Pathological conditions, including hypertension, hyperglycemia, and hyperlipidemia, induce metabolic reprogramming in these cells, altering the balance among glycolysis, fatty acid oxidation, and amino acid metabolism. This reprogramming drives endothelial dysfunction, characterized by reduced nitric oxide (NO) levels, increased inflammation and oxidative stress, and a weakened vascular barrier, thereby accelerating the progression of atherosclerosis, myocardial infarction, calcific aortic valve disease, and aortic aneurysms. Altered metabolites, such as lactate and acetyl-CoA, further exacerbate injury by modulating epigenetic changes and cell signaling. Endothelial metabolism has emerged as a promising therapeutic target for cardiovascular diseases. Natural compounds such as resveratrol, quercetin, and curcumin enhance NO production and reduce oxidative stress. Traditional Chinese medicine formulations (e.g., Qili Qiangxin and Tongxinluo capsules) help regulate glucose and lipid metabolism, thereby mitigating mitochondrial dysfunction and inflammation. Synthetic drugs, including metformin, sodium\u2013glucose transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and experimental agents such as I-152, protect vessels by restoring metabolic homeostasis and endothelial function. Future research integrating multi-omics technologies and artificial intelligence is expected to enable real-time metabolic monitoring and precision interventions. Emerging delivery systems, such as exosome-based approaches and stem cell therapies, offer additional therapeutic potential. A deeper understanding of endothelial metabolic reprogramming will provide novel targets for preventing and treating cardiovascular diseases, thereby advancing precision medicine.<\/jats:p>","DOI":"10.31083\/rcm51541","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:57:11Z","timestamp":1790693831000},"source":"Crossref","is-referenced-by-count":0,"title":["Endothelial Dysfunction and Metabolic Reprogramming in Cardiovascular Diseases"],"prefix":"10.31083","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9231-5276","authenticated-orcid":true,"given":"Hongyu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 210008 Nanjing, Jiangsu, China"},{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2818-6755","authenticated-orcid":true,"given":"Yingliang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 210008 Nanjing, Jiangsu, China"},{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7549-6505","authenticated-orcid":true,"given":"Chengxin","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 210008 Nanjing, Jiangsu, China"},{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6750-8326","authenticated-orcid":true,"given":"Jianing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 210008 Nanjing, Jiangsu, China"},{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1038-7411","authenticated-orcid":true,"given":"Zhihua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"},{"name":"Institute of Cardiothoracic Vascular Disease, Nanjing University, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7451-116X","authenticated-orcid":true,"given":"Hanzhang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"},{"name":"Institute of Cardiothoracic Vascular Disease, Nanjing University, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8044-0117","authenticated-orcid":true,"given":"Shaopeng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"},{"name":"Institute of Cardiothoracic Vascular Disease, Nanjing University, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8617-1435","authenticated-orcid":true,"given":"Yilin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"},{"name":"Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9571-9791","authenticated-orcid":true,"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"},{"name":"Institute of Cardiothoracic Vascular Disease, Nanjing University, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8780-0013","authenticated-orcid":true,"given":"Dongjin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"},{"name":"Institute of Cardiothoracic Vascular Disease, Nanjing University, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9448-5875","authenticated-orcid":true,"given":"Hoshun","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"},{"name":"Institute of Cardiothoracic Vascular Disease, Nanjing University, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2259-3351","authenticated-orcid":true,"given":"Chuiyu","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 210008 Nanjing, Jiangsu, China"},{"name":"Institute of Cardiothoracic Vascular Disease, Nanjing University, 210008 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Schoors S, Bruning U, Missiaen R, Queiroz KC, Borgers G, Elia I, et al. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature. 2015; 520: 192\u2013197.","DOI":"10.1038\/nature14362"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Li Y, Cao GY, Jing WZ, Liu J, Liu M. Global trends and regional differences in incidence and mortality of cardiovascular disease, 1990-2019: findings from 2019 global burden of disease study. European Journal of Preventive Cardiology. 2023; 30: 276\u2013286.","DOI":"10.1093\/eurjpc\/zwac285"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Trimm E, Red-Horse K. Vascular endothelial cell development and diversity. Nature Reviews. Cardiology. 2023; 20: 197\u2013210.","DOI":"10.1038\/s41569-022-00770-1"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980; 288: 373\u2013376.","DOI":"10.1038\/288373a0"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Tamargo IA, Baek KI, Kim Y, Park C, Jo H. Flow-induced reprogramming of endothelial cells in atherosclerosis. Nature Reviews. Cardiology. 2023; 20: 738\u2013753.","DOI":"10.1038\/s41569-023-00883-1"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Liu Y, Wu Z, Li Y, Chen Y, Zhao X, Wu M, et al. Metabolic reprogramming and interventions in angiogenesis. Journal of Advanced Research. 2025; 70: 323\u2013338.","DOI":"10.1016\/j.jare.2024.05.001"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Missiaen R, Morales-Rodriguez F, Eelen G, Carmeliet P. Targeting endothelial metabolism for anti-angiogenesis therapy: A pharmacological perspective. Vascular Pharmacology. 2017; 90: 8\u201318.","DOI":"10.1016\/j.vph.2017.01.001"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Stroope C, Nettersheim FS, Coon B, Finney AC, Schwartz MA, Ley K, et al. Dysregulated cellular metabolism in atherosclerosis: mediators and therapeutic opportunities. Nature Metabolism. 2024; 6: 617\u2013638.","DOI":"10.1038\/s42255-024-01015-w"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Zhang Y, Ma KL, Gong YX, Wang GH, Hu ZB, Liu L, et al. Platelet Microparticles Mediate Glomerular Endothelial Injury in Early Diabetic Nephropathy. Journal of the American Society of Nephrology. 2018; 29: 2671\u20132695.","DOI":"10.1681\/ASN.2018040368"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Bozkurt B, Aguilar D, Deswal A, Dunbar SB, Francis GS, Horwich T, et al. Contributory Risk and Management of Comorbidities of Hypertension, Obesity, Diabetes Mellitus, Hyperlipidemia, and Metabolic Syndrome in Chronic Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2016; 134: e535\u2013e578.","DOI":"10.1161\/CIR.0000000000000450"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Li M, Wu Y, Ye L. The Role of Amino Acids in Endothelial Biology and Function. Cells. 2022; 11: 1372.","DOI":"10.3390\/cells11081372"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Durante W. Glutamine Deficiency Promotes Immune and Endothelial Cell Dysfunction in COVID-19. International Journal of Molecular Sciences. 2023; 24: 7593.","DOI":"10.3390\/ijms24087593"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Zhao M, Zhou J, Hu Y, Wang X, An J, Liu M, et al. Defective Endothelial Glutaminolysis Contributes to Impaired Angiogenesis and Poor Ischemic Tissue Repair in Diabetes. Research. 2025; 8: 0706.","DOI":"10.34133\/research.0706"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Citrin KM, Chaube B, Fern\u00e1ndez-Hernando C, Su\u00e1rez Y. Intracellular endothelial cell metabolism in vascular function and dysfunction. Trends in Endocrinology and Metabolism: TEM. 2025; 36: 744\u2013755.","DOI":"10.1016\/j.tem.2024.11.004"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Herrle N, Malacarne PF, Warwick T, Cabrera-Orefice A, Chen Y, Gheisari M, et al. The transaminase-\u03c9-amidase pathway senses oxidative stress to control glutamine metabolism and \u03b1-ketoglutarate levels in endothelial cells. The EMBO Journal. 2026; 45: 820\u2013855.","DOI":"10.1038\/s44318-025-00642-7"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Kalucka J, Bierhansl L, Conchinha NV, Missiaen R, Elia I, Br\u00fcning U, et al. Quiescent Endothelial Cells Upregulate Fatty Acid \u03b2-Oxidation for Vasculoprotection via Redox Homeostasis. Cell Metabolism. 2018; 28: 881\u2013894.e13.","DOI":"10.1016\/j.cmet.2018.07.016"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Liu B, Dai Z. Fatty Acid Metabolism in Endothelial Cell. Genes. 2022; 13: 2301.","DOI":"10.3390\/genes13122301"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Ghosh A, Gao L, Thakur A, Siu PM, Lai CWK. Role of free fatty acids in endothelial dysfunction. Journal of Biomedical Science. 2017; 24: 50.","DOI":"10.1186\/s12929-017-0357-5"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Zhang Y, Zhao J, Ren C, Hu B, Ding R, He Z, et al. Free fatty acids induce coronary microvascular dysfunction via inhibition of the AMPK\/KLF2\/eNOS signaling pathway. International Journal of Molecular Medicine. 2023; 51: 34.","DOI":"10.3892\/ijmm.2023.5237"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Schoors S, De Bock K, Cantelmo AR, Georgiadou M, Ghesqui\u00e8re B, Cauwenberghs S, et al. Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis. Cell Metabolism. 2014; 19: 37\u201348.","DOI":"10.1016\/j.cmet.2013.11.008"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Paul D, Bolhuis DL, Yan H, Das S, Xu X, Abbate CC, et al. Transient APC\/C inactivation by mTOR boosts glycolysis during cell cycle entry. Nature. 2025; 646: 198\u2013207.","DOI":"10.1038\/s41586-025-09328-w"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Bu Y, Wu H, Deng R, Wang Y, Gan P, Dong X, et al. Geniposide Improves Glycolysis Driven Angiogenesis in Experimentary Arthritis by Inhibiting SphK1-PI3K-Akt-PFKFB3 Signal. Phytotherapy Research. 2025; 39: 3419\u20133431.","DOI":"10.1002\/ptr.70019"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Eelen G, de Zeeuw P, Treps L, Harjes U, Wong BW, Carmeliet P. Endothelial Cell Metabolism. Physiological Reviews. 2018; 98: 3\u201358.","DOI":"10.1152\/physrev.00001.2017"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Rohlenova K, Veys K, Miranda-Santos I, De Bock K, Carmeliet P. Endothelial Cell Metabolism in Health and Disease. Trends in Cell Biology. 2018; 28: 224\u2013236.","DOI":"10.1016\/j.tcb.2017.10.010"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Eelen G, de Zeeuw P, Simons M, Carmeliet P. Endothelial cell metabolism in normal and diseased vasculature. Circulation Research. 2015; 116: 1231\u20131244.","DOI":"10.1161\/CIRCRESAHA.116.302855"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Du W, Ren L, Hamblin MH, Fan Y. Endothelial Cell Glucose Metabolism and Angiogenesis. Biomedicines. 2021; 9: 147.","DOI":"10.3390\/biomedicines9020147"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Chen J, Huang Z, Chen Y, Tian H, Chai P, Shen Y, et al. Lactate and lactylation in cancer. Signal Transduction and Targeted Therapy. 2025; 10: 38.","DOI":"10.1038\/s41392-024-02082-x"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Li X, Yang Y, Zhang B, Lin X, Fu X, An Y, et al. Lactate metabolism in human health and disease. Signal Transduction and Targeted Therapy. 2022; 7: 305.","DOI":"10.1038\/s41392-022-01151-3"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"TeSlaa T, Ralser M, Fan J, Rabinowitz JD. The pentose phosphate pathway in health and disease. Nature Metabolism. 2023; 5: 1275\u20131289.","DOI":"10.1038\/s42255-023-00863-2"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Chatham JC, N\u00f6t LG, F\u00fcl\u00f6p N, Marchase RB. Hexosamine biosynthesis and protein O-glycosylation: the first line of defense against stress, ischemia, and trauma. Shock. 2008; 29: 431\u2013440.","DOI":"10.1097\/shk.0b013e3181598bad"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Yang K, Velagapudi S, Akhmedov A, Kraler S, Lapikova-Bryhinska T, Schmiady MO, et al. Chronic SIRT1 supplementation in diabetic mice improves endothelial function by suppressing oxidative stress. Cardiovascular Research. 2023; 119: 2190\u20132201.","DOI":"10.1093\/cvr\/cvad102"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Ying W. NAD+\/NADH and NADP+\/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxidants & Redox Signaling. 2008; 10: 179\u2013206.","DOI":"10.1089\/ars.2007.1672"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Jongkind JF, Verkerk A, Baggen RG. Glutathione metabolism of human vascular endothelial cells under peroxidative stress. Free Radical Biology & Medicine. 1989; 7: 507\u2013512.","DOI":"10.1016\/0891-5849(89)90026-9"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Chen Z, Zhang Y, Qian C, Xia L. The Role of the Pentose Phosphate Pathway in Cardiovascular Diseases. Cardiovascular Drugs and Therapy. 2026; 40: 1125\u20131143.","DOI":"10.1007\/s10557-025-07788-w"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Chatham JC, Zhang J, Wende AR. Role of O-Linked N-Acetylglucosamine Protein Modification in Cellular (Patho)Physiology. Physiological Reviews. 2021; 101: 427\u2013493.","DOI":"10.1152\/physrev.00043.2019"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Liu J, Li K, Yi Z, Saqirile, Wang C, Yang R. Oxidative-Inflammatory Crosstalk and Multi-Target Natural Agents: Decoding Diabetic Vascular Complications. Current Issues in Molecular Biology. 2025; 47: 614.","DOI":"10.3390\/cimb47080614"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Bierhaus A, Schiekofer S, Schwaninger M, Andrassy M, Humpert PM, Chen J, et al. Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. Diabetes. 2001; 50: 2792\u20132808.","DOI":"10.2337\/diabetes.50.12.2792"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Liang K. Mitochondrial CPT1A: Insights into structure, function, and basis for drug development. Frontiers in Pharmacology. 2023; 14: 1160440.","DOI":"10.3389\/fphar.2023.1160440"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Schreurs M, Kuipers F, van der Leij FR. Regulatory enzymes of mitochondrial beta-oxidation as targets for treatment of the metabolic syndrome. Obesity Reviews. 2010; 11: 380\u2013388.","DOI":"10.1111\/j.1467-789X.2009.00642.x"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Brownsey RW, Boone AN, Elliott JE, Kulpa JE, Lee WM. Regulation of acetyl-CoA carboxylase. Biochemical Society Transactions. 2006; 34: 223\u2013227.","DOI":"10.1042\/BST20060223"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Curthoys NP, Watford M. Regulation of glutaminase activity and glutamine metabolism. Annual Review of Nutrition. 1995; 15: 133\u2013159.","DOI":"10.1146\/annurev.nu.15.070195.001025"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009; 136: 521\u2013534.","DOI":"10.1016\/j.cell.2008.11.044"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Chen TH, Wang HC, Chang CJ, Lee SY. Mitochondrial Glutathione in Cellular Redox Homeostasis and Disease Manifestation. International Journal of Molecular Sciences. 2024; 25: 1314.","DOI":"10.3390\/ijms25021314"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Huang H, Vandekeere S, Kalucka J, Bierhansl L, Zecchin A, Br\u00fcning U, et al. Role of glutamine and interlinked asparagine metabolism in vessel formation. The EMBO Journal. 2017; 36: 2334\u20132352.","DOI":"10.15252\/embj.201695518"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Labarrere CA, Kassab GS. Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation. Frontiers in Nutrition. 2022; 9: 1007816.","DOI":"10.3389\/fnut.2022.1007816"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Draoui N, de Zeeuw P, Carmeliet P. Angiogenesis revisited from a metabolic perspective: role and therapeutic implications of endothelial cell metabolism. Open Biology. 2017; 7: 170219.","DOI":"10.1098\/rsob.170219"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Morrison RF, Seidel ER. Vascular endothelial cell proliferation: regulation of cellular polyamines. Cardiovascular Research. 1995; 29: 841\u2013847.","DOI":"10.1016\/S0008-6363(96)88621-4"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Morgan DM. Polyamines, arginine and nitric oxide. Biochemical Society Transactions. 1994; 22: 879\u2013883.","DOI":"10.1042\/bst0220879"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Yu W, Wang Z, Zhang K, Chi Z, Xu T, Jiang D, et al. One-Carbon Metabolism Supports S-Adenosylmethionine and Histone Methylation to Drive Inflammatory Macrophages. Molecular Cell. 2019; 75: 1147\u20131160.e5.","DOI":"10.1016\/j.molcel.2019.06.039"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"McGarry JD, Foster DW. Regulation of hepatic fatty acid oxidation and ketone body production. Annual Review of Biochemistry. 1980; 49: 395\u2013420.","DOI":"10.1146\/annurev.bi.49.070180.002143"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Richards J, El-Hamamsy I, Chen S, Sarang Z, Sarathchandra P, Yacoub MH, et al. Side-specific endothelial-dependent regulation of aortic valve calcification: interplay of hemodynamics and nitric oxide signaling. The American Journal of Pathology. 2013; 182: 1922\u20131931.","DOI":"10.1016\/j.ajpath.2013.01.037"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Fern\u00e1ndez Esmerats J, Heath J, Jo H. Shear-Sensitive Genes in Aortic Valve Endothelium. Antioxidants & Redox Signaling. 2016; 25: 401\u2013414.","DOI":"10.1089\/ars.2015.6554"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Singh T, Jacobs KA, Polacheck WJ, Kutys ML. The Notch1 intracellular domain orchestrates mechanotransduction of fluid shear stress. Life Science Alliance. 2026; 9: e202503599.","DOI":"10.26508\/lsa.202503599"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Hulin A, Hego A, Lancellotti P, Oury C. Advances in Pathophysiology of Calcific Aortic Valve Disease Propose Novel Molecular Therapeutic Targets. Frontiers in Cardiovascular Medicine. 2018; 5: 21.","DOI":"10.3389\/fcvm.2018.00021"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C, et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circulation. Cardiovascular Genetics. 2010; 3: 207\u2013214.","DOI":"10.1161\/CIRCGENETICS.109.852814"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Ma W, Heianza Y, Huang T, Wang T, Sun D, Zheng Y, et al. Dietary glutamine, glutamate and mortality: two large prospective studies in US men and women. International Journal of Epidemiology. 2018; 47: 311\u2013320.","DOI":"10.1093\/ije\/dyx234"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Murcy F, Borowczyk C, Gourion-Arsiquaud S, Torrino S, Ouahrouche N, Barouillet T, et al. GLS2 links glutamine metabolism and atherosclerosis by remodeling artery walls. Nature Cardiovascular Research. 2024; 3: 1454\u20131467.","DOI":"10.1038\/s44161-024-00566-1"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Cao X, Wu VWY, Han Y, Hong H, Wu Y, Kong APS, et al. Role of Argininosuccinate Synthase 1 -Dependent L-Arginine Biosynthesis in the Protective Effect of Endothelial Sirtuin 3 Against Atherosclerosis. Advanced Science. 2024; 11: e2307256.","DOI":"10.1002\/advs.202307256"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"Anand SK, Governale TA, Zhang X, Razani B, Yurdagul A Jr, Pattillo CB, et al. Amino Acid Metabolism and Atherosclerotic Cardiovascular Disease. The American Journal of Pathology. 2024; 194: 510\u2013524.","DOI":"10.1016\/j.ajpath.2023.12.006"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"Reho JJ, Guo DF, Rahmouni K. Mechanistic Target of Rapamycin Complex 1 Signaling Modulates Vascular Endothelial Function Through Reactive Oxygen Species. Journal of the American Heart Association. 2019; 8: e010662.","DOI":"10.1161\/JAHA.118.010662"},{"key":"ref61","doi-asserted-by":"publisher","unstructured":"Jang C, Oh SF, Wada S, Rowe GC, Liu L, Chan MC, et al. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nature Medicine. 2016; 22: 421\u2013426.","DOI":"10.1038\/nm.4057"},{"key":"ref62","doi-asserted-by":"publisher","unstructured":"Sansbury BE, DeMartino AM, Xie Z, Brooks AC, Brainard RE, Watson LJ, et al. Metabolomic analysis of pressure-overloaded and infarcted mouse hearts. Circulation. Heart Failure. 2014; 7: 634\u2013642.","DOI":"10.1161\/CIRCHEARTFAILURE.114.001151"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"St\u00fchlinger MC, Tsao PS, Her JH, Kimoto M, Balint RF, Cooke JP. Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine. Circulation. 2001; 104: 2569\u20132575.","DOI":"10.1161\/hc4601.098514"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"Hofmann MA, Lalla E, Lu Y, Gleason MR, Wolf BM, Tanji N, et al. Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. The Journal of Clinical Investigation. 2001; 107: 675\u2013683.","DOI":"10.1172\/JCI10588"},{"key":"ref65","doi-asserted-by":"publisher","unstructured":"Yin YL, Chen Y, Ren F, Wang L, Zhu ML, Lu JX, et al. Nitrosative stress induced by homocysteine thiolactone drives vascular cognitive impairments via GTP cyclohydrolase 1 S-nitrosylation in vivo. Redox Biology. 2022; 58: 102540.","DOI":"10.1016\/j.redox.2022.102540"},{"key":"ref66","doi-asserted-by":"publisher","unstructured":"Arefin S, L\u00f6fgren L, Stenvinkel P, Granqvist AB, Kublickiene K. Associations of Biopterins and ADMA with Vascular Function in Peripheral Microcirculation from Patients with Chronic Kidney Disease. International Journal of Molecular Sciences. 2023; 24: 5582.","DOI":"10.3390\/ijms24065582"},{"key":"ref67","doi-asserted-by":"publisher","unstructured":"Sonkar SK, Verma J, Sonkar GK, Gupta A, Singh A, Vishwakarma P, et al. Assessing the Role of Asymmetric Dimethylarginine in Endothelial Dysfunction: Insights Into Cardiovascular Risk Factors. Cureus. 2025; 17: e77565.","DOI":"10.7759\/cureus.77565"},{"key":"ref68","doi-asserted-by":"publisher","unstructured":"Harvey KA, Walker CL, Pavlina TM, Xu Z, Zaloga GP, Siddiqui RA. Long-chain saturated fatty acids induce pro-inflammatory responses and impact endothelial cell growth. Clinical Nutrition. 2010; 29: 492\u2013500.","DOI":"10.1016\/j.clnu.2009.10.008"},{"key":"ref69","doi-asserted-by":"publisher","unstructured":"Su Z, Wang J, Xiao C, Zhong W, Liu J, Liu X, et al. Functional role of Ash2l in oxLDL induced endothelial dysfunction and atherosclerosis. Cellular and Molecular Life Sciences. 2024; 81: 62.","DOI":"10.1007\/s00018-024-05130-5"},{"key":"ref70","doi-asserted-by":"publisher","unstructured":"Chiu TH, Ku CW, Ho TJ, Tsai KL, Yang YD, Ou HC, et al. Schisanhenol ameliorates oxLDL-caused endothelial dysfunction by inhibiting LOX-1 signaling. Environmental Toxicology. 2023; 38: 1589\u20131596.","DOI":"10.1002\/tox.23788"},{"key":"ref71","doi-asserted-by":"publisher","unstructured":"Munno M, Mallia A, Greco A, Modafferi G, Banfi C, Eligini S. Radical Oxygen Species, Oxidized Low-Density Lipoproteins, and Lectin-like Oxidized Low-Density Lipoprotein Receptor 1: A Vicious Circle in Atherosclerotic Process. Antioxidants. 2024; 13: 583.","DOI":"10.3390\/antiox13050583"},{"key":"ref72","doi-asserted-by":"publisher","unstructured":"Hung CH, Chan SH, Chu PM, Tsai KL. Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation. Molecular Nutrition & Food Research. 2015; 59: 1905\u20131917.","DOI":"10.1002\/mnfr.201500144"},{"key":"ref73","doi-asserted-by":"publisher","unstructured":"Thengchaisri N, Kuo L, Hein TW. H2O2 Mediates VEGF- and Flow-Induced Dilations of Coronary Arterioles in Early Type 1 Diabetes: Role of Vascular Arginase and PI3K-Linked eNOS Uncoupling. International Journal of Molecular Sciences. 2022; 24: 489.","DOI":"10.3390\/ijms24010489"},{"key":"ref74","doi-asserted-by":"publisher","unstructured":"P\u00e9rez L, Vallejos A, Echeverria C, Varela D, Cabello-Verrugio C, Simon F. OxHDL controls LOX-1 expression and plasma membrane localization through a mechanism dependent on NOX\/ROS\/NF-\u03baB pathway on endothelial cells. Laboratory Investigation; a Journal of Technical Methods and Pathology. 2019; 99: 421\u2013437.","DOI":"10.1038\/s41374-018-0151-3"},{"key":"ref75","doi-asserted-by":"publisher","unstructured":"Wu X, Ye J, Cai W, Yang X, Zou Q, Lin J, et al. LDHA mediated degradation of extracellular matrix is a potential target for the treatment of aortic dissection. Pharmacological Research. 2022; 176: 106051.","DOI":"10.1016\/j.phrs.2021.106051"},{"key":"ref76","doi-asserted-by":"publisher","unstructured":"Wang Q, Yesitayi G, Liu B, Siti D, Ainiwan M, Aizitiaili A, et al. Targeting metabolism in aortic aneurysm and dissection: from basic research to clinical applications. International Journal of Biological Sciences. 2023; 19: 3869\u20133891.","DOI":"10.7150\/ijbs.85467"},{"key":"ref77","doi-asserted-by":"publisher","unstructured":"Liu Z, Feng G, Chen Y, Fan J, Liang Z, Bi J, et al. Hyperhomocysteinemia may aggravate abdominal aortic aneurysm formation by up-regulating RASSF2. Gene. 2024; 898: 148036.","DOI":"10.1016\/j.gene.2023.148036"},{"key":"ref78","doi-asserted-by":"publisher","unstructured":"Liu Z, Dong N, Hui H, Wang Y, Liu F, Xu L, et al. Endothelial cell-derived tetrahydrobiopterin prevents aortic valve calcification. European Heart Journal. 2022; 43: 1652\u20131664.","DOI":"10.1093\/eurheartj\/ehac037"},{"key":"ref79","doi-asserted-by":"publisher","unstructured":"Zhang J, Lei W, Zhou J, Zhang Y, Huang F, Chen M. Uric acid promotes aortic valve calcification via mediating valve interstitial cell osteogenic differentiation and endothelial dysfunction. FASEB Journal. 2025; 39: e70437.","DOI":"10.1096\/fj.202402831R"},{"key":"ref80","doi-asserted-by":"publisher","unstructured":"Zhong G, Su S, Li J, Zhao H, Hu D, Chen J, et al. Activation of Piezo1 promotes osteogenic differentiation of aortic valve interstitial cell through YAP-dependent glutaminolysis. Science Advances. 2023; 9: eadg0478.","DOI":"10.1126\/sciadv.adg0478"},{"key":"ref81","doi-asserted-by":"publisher","unstructured":"Zhili G, Zhimin G, Nenghua Z. Role of vascular endothelial dysfunction and metabolic eprogramming of immune cells in the development and ogression of atherosclerosis. Frontiers in Physiology. 2025; 16: 1624225.","DOI":"10.3389\/fphys.2025.1624225"},{"key":"ref82","doi-asserted-by":"publisher","unstructured":"Kheradmand M, Sangha G, Sissons CM, Sun M, Zhou X, Smith LV, et al. Glutamine enhances endothelial cell survival and vasodilation by increasing glutathione to reduce oxidative stress. Physiological Reports. 2026; 14: e70737.","DOI":"10.14814\/phy2.70737"},{"key":"ref83","doi-asserted-by":"publisher","unstructured":"Zheng Y, Hu FB, Ruiz-Canela M, Clish CB, Dennis C, Salas-Salvado J, et al. Metabolites of Glutamate Metabolism Are Associated With Incident Cardiovascular Events in the PREDIMED PREvenci\u00f3n con DIeta MEDiterr\u00e1nea (PREDIMED) Trial. Journal of the American Heart Association. 2016; 5: e003755.","DOI":"10.1161\/JAHA.116.003755"},{"key":"ref84","doi-asserted-by":"publisher","unstructured":"McGettrick AF, O'Neill LAJ. The Role of HIF in Immunity and Inflammation. Cell Metabolism. 2020; 32: 524\u2013536.","DOI":"10.1016\/j.cmet.2020.08.002"},{"key":"ref85","doi-asserted-by":"publisher","unstructured":"Zeng H, Pan T, Zhan M, Hailiwu R, Liu B, Yang H, et al. Suppression of PFKFB3-driven glycolysis restrains endothelial-to-mesenchymal transition and fibrotic response. Signal Transduction and Targeted Therapy. 2022; 7: 303.","DOI":"10.1038\/s41392-022-01097-6"},{"key":"ref86","doi-asserted-by":"publisher","unstructured":"Hernandez-Navarro I, Botana L, Diez-Mata J, Tesoro L, Jimenez-Guirado B, Gonzalez-Cucharero C, et al. Replicative Endothelial Cell Senescence May Lead to Endothelial Dysfunction by Increasing the BH2\/BH4 Ratio Induced by Oxidative Stress, Reducing BH4 Availability, and Decreasing the Expression of eNOS. International Journal of Molecular Sciences. 2024; 25: 9890.","DOI":"10.3390\/ijms25189890"},{"key":"ref87","doi-asserted-by":"publisher","unstructured":"Zhenyukh O, Gonz\u00e1lez-Amor M, Rodrigues-Diez RR, Esteban V, Ruiz-Ortega M, Salaices M, et al. Branched-chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation. Journal of Cellular and Molecular Medicine. 2018; 22: 4948\u20134962.","DOI":"10.1111\/jcmm.13759"},{"key":"ref88","doi-asserted-by":"publisher","unstructured":"Wang W, Zhang F, Xia Y, Zhao S, Yan W, Wang H, et al. Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction. American Journal of Physiology. Heart and Circulatory Physiology. 2016; 311: H1160\u2013H1169.","DOI":"10.1152\/ajpheart.00114.2016"},{"key":"ref89","doi-asserted-by":"publisher","unstructured":"Shi L, Tu BP. Acetyl-CoA and the regulation of metabolism: mechanisms and consequences. Current Opinion in Cell Biology. 2015; 33: 125\u2013131.","DOI":"10.1016\/j.ceb.2015.02.003"},{"key":"ref90","doi-asserted-by":"publisher","unstructured":"Bruschi M, Biancucci F, Masini S, Piacente F, Ligi D, Bartoccini F, et al. The influence of redox modulation on hypoxic endothelial cell metabolic and proteomic profiles through a small thiol-based compound tuning glutathione and thioredoxin systems. BioFactors. 2023; 49: 1205\u20131222.","DOI":"10.1002\/biof.1988"},{"key":"ref91","doi-asserted-by":"publisher","unstructured":"Song C, Sha T, Liu C, Li J. Calcific aortic valve disease: can targeting endothelial-mesenchymal transition be a new alternative to surgery?-a narrative review. Cardiovascular Diagnosis and Therapy. 2026; 16: 7.","DOI":"10.21037\/cdt-2025-373"},{"key":"ref92","doi-asserted-by":"publisher","unstructured":"S\u00e1nchez-Esteban S, Castro-Pinto M, Cook-Calvete A, Revent\u00fan P, Delgado-Mar\u00edn M, Benito-Manzanaro L, et al. Integrin-Linked Kinase Expression in Human Valve Endothelial Cells Plays a Protective Role in Calcific Aortic Valve Disease. Antioxidants. 2022; 11: 1736.","DOI":"10.3390\/antiox11091736"},{"key":"ref93","doi-asserted-by":"publisher","unstructured":"Fan L, Yao D, Fan Z, Zhang T, Shen Q, Tong F, et al. Beyond VICs: Shedding light on the overlooked VECs in calcific aortic valve disease. Biomedicine & Pharmacotherapy. 2024; 178: 117143.","DOI":"10.1016\/j.biopha.2024.117143"},{"key":"ref94","doi-asserted-by":"publisher","unstructured":"Alvandi Z, Bischoff J. Endothelial-Mesenchymal Transition in Cardiovascular Disease. Arteriosclerosis, Thrombosis, and Vascular Biology. 2021; 41: 2357\u20132369.","DOI":"10.1161\/ATVBAHA.121.313788"},{"key":"ref95","doi-asserted-by":"publisher","unstructured":"Gimbrone MA Jr, Garc\u00eda-Carde\u00f1a G. Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis. Cardiovascular Pathology. 2013; 22: 9\u201315.","DOI":"10.1016\/j.carpath.2012.06.006"},{"key":"ref96","doi-asserted-by":"publisher","unstructured":"Guo S, Wang L, Cao K, Li Z, Song M, Huang S, et al. Endothelial nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome regulation in atherosclerosis. Cardiovascular Research. 2024; 120: 883\u2013898.","DOI":"10.1093\/cvr\/cvae071"},{"key":"ref97","doi-asserted-by":"publisher","unstructured":"Campagna R, Mazzanti L, Pompei V, Alia S, Vignini A, Emanuelli M. The Multifaceted Role of Endothelial Sirt1 in Vascular Aging: An Update. Cells. 2024; 13: 1469.","DOI":"10.3390\/cells13171469"},{"key":"ref98","doi-asserted-by":"publisher","unstructured":"Lin T, Yang WQ, Luo WW, Zhang LL, Mai YQ, Li ZQ, et al. Disturbance of Fatty Acid Metabolism Promoted Vascular Endothelial Cell Senescence via Acetyl-CoA-Induced Protein Acetylation Modification. Oxidative Medicine and Cellular Longevity. 2022; 2022: 1198607.","DOI":"10.1155\/2022\/1198607"},{"key":"ref99","doi-asserted-by":"publisher","unstructured":"Zhang Y, Zhu Z, Cao Y, Xiong Z, Duan Y, Lin J, et al. Rnd3 suppresses endothelial cell pyroptosis in atherosclerosis through regulation of ubiquitination of TRAF6. Clinical and Translational Medicine. 2023; 13: e1406.","DOI":"10.1002\/ctm2.1406"},{"key":"ref100","doi-asserted-by":"publisher","unstructured":"Maino A, Walsh JL, Portolan L, Kotronias R, Ameri P, Vergallo R, et al. Therapeutic interventions for coronary microvascular obstruction after acute myocardial infarction: Developments and challenges. Pharmacology & Therapeutics. 2026; 282: 108995.","DOI":"10.1016\/j.pharmthera.2026.108995"},{"key":"ref101","doi-asserted-by":"publisher","unstructured":"Nicolau AM, Silva PG, Mej\u00eda HPG, Granada JF, Kaluza GL, Burkhoff D, et al. Molecular Mechanisms of Microvascular Obstruction and Dysfunction in Percutaneous Coronary Interventions: From Pathophysiology to Therapeutics-A Comprehensive Review. International Journal of Molecular Sciences. 2025; 26: 6835.","DOI":"10.3390\/ijms26146835"},{"key":"ref102","doi-asserted-by":"publisher","unstructured":"Boutagy NE, Gamez-Mendez A, Fowler JW, Zhang H, Chaube BK, Esplugues E, et al. Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice. The Journal of Clinical Investigation. 2024; 134: e170453.","DOI":"10.1172\/JCI170453"},{"key":"ref103","doi-asserted-by":"publisher","unstructured":"Cominacini L, Pasini AF, Garbin U, Davoli A, Tosetti ML, Campagnola M, et al. Oxidized low density lipoprotein (ox-LDL) binding to ox-LDL receptor-1 in endothelial cells induces the activation of NF-kappaB through an increased production of intracellular reactive oxygen species. The Journal of Biological Chemistry. 2000; 275: 12633\u201312638.","DOI":"10.1074\/jbc.275.17.12633"},{"key":"ref104","doi-asserted-by":"publisher","unstructured":"Yang K, Cui S, Wang J, Xu T, Du H, Yue H, et al. Early Progression of Abdominal Aortic Aneurysm is Decelerated by Improved Endothelial Barrier Function via ALDH2-LIN28B-ELK3 Signaling. Advanced Science. 2023; 10: e2302231.","DOI":"10.1002\/advs.202302231"},{"key":"ref105","doi-asserted-by":"publisher","unstructured":"Watanabe H, Kuhne W, Spahr R, Schwartz P, Piper HM. Macromolecule permeability of coronary and aortic endothelial monolayers under energy depletion. The American Journal of Physiology. 1991; 260: H1344\u20131352.","DOI":"10.1152\/ajpheart.1991.260.4.H1344"},{"key":"ref106","doi-asserted-by":"publisher","unstructured":"V\u00edtkov\u00e1 V, \u017divn\u00fd J, Janota J. Endothelial cell-derived microvesicles: potential mediators and biomarkers of pathologic processes. Biomarkers in Medicine. 2018; 12: 161\u2013175.","DOI":"10.2217\/bmm-2017-0182"},{"key":"ref107","doi-asserted-by":"publisher","unstructured":"Zhao H, Han L, Jian Y, Ma Y, Yan W, Chen X, et al. Resveratrol induces apoptosis in human melanoma cell through negatively regulating Erk\/PKM2\/Bcl-2 axis. OncoTargets and Therapy. 2018; 11: 8995\u20139006.","DOI":"10.2147\/OTT.S186247"},{"key":"ref108","doi-asserted-by":"publisher","unstructured":"Pan H, Wu Z, Gao Y, Yao W, Feng G, Wang H. The relevance of resveratrol in ameliorating carotid atherosclerosis through glycolysis. BMC Cardiovascular Disorders. 2025; 25: 301.","DOI":"10.1186\/s12872-025-04735-3"},{"key":"ref109","doi-asserted-by":"publisher","unstructured":"Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. Quercetin reduces blood pressure in hypertensive subjects. The Journal of Nutrition. 2007; 137: 2405\u20132411.","DOI":"10.1093\/jn\/137.11.2405"},{"key":"ref110","doi-asserted-by":"publisher","unstructured":"Mad Azli AA, Salamt N, Aminuddin A, Roos NAC, Mokhtar MH, Kumar J, et al. The Role of Curcumin in Modulating Vascular Function and Structure during Menopause: A Systematic Review. Biomedicines. 2024; 12: 2281.","DOI":"10.3390\/biomedicines12102281"},{"key":"ref111","doi-asserted-by":"publisher","unstructured":"Wang Y, Han X, Fu M, Wang J, Song Y, Liu Y, et al. Qiliqiangxin attenuates hypoxia-induced injury in primary rat cardiac microvascular endothelial cells via promoting HIF-1\u03b1-dependent glycolysis. Journal of Cellular and Molecular Medicine. 2018; 22: 2791\u20132803.","DOI":"10.1111\/jcmm.13572"},{"key":"ref112","doi-asserted-by":"publisher","unstructured":"Jiang X, Ma C, Gao Y, Cui H, Zheng Y, Li J, et al. Tongxinluo attenuates atherosclerosis by inhibiting ROS\/NLRP3\/caspase-1-mediated endothelial cell pyroptosis. Journal of Ethnopharmacology. 2023; 304: 116011.","DOI":"10.1016\/j.jep.2022.116011"},{"key":"ref113","doi-asserted-by":"publisher","unstructured":"Zhao Y, Shao C, Zhou H, Yu L, Bao Y, Mao Q, et al. Salvianolic acid B inhibits atherosclerosis and TNF-\u03b1-induced inflammation by regulating NF-\u03baB\/NLRP3 signaling pathway. Phytomedicine. 2023; 119: 155002.","DOI":"10.1016\/j.phymed.2023.155002"},{"key":"ref114","doi-asserted-by":"publisher","unstructured":"Sun C, Su S, Zhu Y, Guo J, Guo S, Qian D, et al. Salvia miltiorrhiza stem-leaf active components of salvianolic acids and flavonoids improved the hemorheological disorder and vascular endothelial function on microcirculation dysfunction rats. Phytotherapy Research. 2020; 34: 1704\u20131720.","DOI":"10.1002\/ptr.6652"},{"key":"ref115","doi-asserted-by":"publisher","unstructured":"Xiang J, Zhang C, Di T, Chen L, Zhao W, Wei L, et al. Salvianolic acid B alleviates diabetic endothelial and mitochondrial dysfunction by down-regulating apoptosis and mitophagy of endothelial cells. Bioengineered. 2022; 13: 3486\u20133502.","DOI":"10.1080\/21655979.2022.2026552"},{"key":"ref116","doi-asserted-by":"publisher","unstructured":"Ko YS, Jin H, Park SW, Kim HJ. Salvianolic acid B protects against oxLDL-induced endothelial dysfunction under high-glucose conditions by downregulating ROCK1-mediated mitophagy and apoptosis. Biochemical Pharmacology. 2020; 174: 113815.","DOI":"10.1016\/j.bcp.2020.113815"},{"key":"ref117","doi-asserted-by":"publisher","unstructured":"Shang D, Zhang X, Liu H, Tu Z. Suppressing endothelial senescence: A comprehensive analysis of metformin's mechanisms and implications. Life Sciences. 2025; 376: 123730.","DOI":"10.1016\/j.lfs.2025.123730"},{"key":"ref118","doi-asserted-by":"publisher","unstructured":"Ding Y, Zhou Y, Ling P, Feng X, Luo S, Zheng X, et al. Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function. Theranostics. 2021; 11: 9376\u20139396.","DOI":"10.7150\/thno.64706"},{"key":"ref119","doi-asserted-by":"publisher","unstructured":"Wang W, Li Y, Zhang Y, Ye T, Wang K, Li S, et al. SIRT1 mediates the inhibitory effect of Dapagliflozin on EndMT by inhibiting the acetylation of endothelium Notch1. Cardiovascular Diabetology. 2023; 22: 331.","DOI":"10.1186\/s12933-023-02040-x"},{"key":"ref120","doi-asserted-by":"publisher","unstructured":"Dyck JRB, Sossalla S, Hamdani N, Coronel R, Weber NC, Light PE, et al. Cardiac mechanisms of the beneficial effects of SGLT2 inhibitors in heart failure: Evidence for potential off-target effects. Journal of Molecular and Cellular Cardiology. 2022; 167: 17\u201331.","DOI":"10.1016\/j.yjmcc.2022.03.005"},{"key":"ref121","doi-asserted-by":"publisher","unstructured":"Li G, Hou N, Liu H, Li J, Deng H, Lan H, et al. Dapagliflozin alleviates high glucose-induced injury of endothelial cells via inducing autophagy. Clinical and Experimental Pharmacology & Physiology. 2024; 51: e13846.","DOI":"10.1111\/1440-1681.13846"},{"key":"ref122","doi-asserted-by":"publisher","unstructured":"Ma L, Zou R, Shi W, Zhou N, Chen S, Zhou H, et al. SGLT2 inhibitor dapagliflozin reduces endothelial dysfunction and microvascular damage during cardiac ischemia\/reperfusion injury through normalizing the XO-SERCA2-CaMKII-coffilin pathways. Theranostics. 2022; 12: 5034\u20135050.","DOI":"10.7150\/thno.75121"},{"key":"ref123","doi-asserted-by":"publisher","unstructured":"Akl MM, Ahmed A. Localized Semaglutide Injection for Hyperinsulinemia-Induced Lymphatic Dysfunction: A Narrative Review Proposing a Promising Metabolic Perspective for Lymphedema Therapy. Advanced Pharmaceutical Bulletin. 2025; 15: 499\u2013505.","DOI":"10.34172\/apb.025.43911"}],"container-title":["Reviews in Cardiovascular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/27\/9\/10.31083\/RCM51541","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:57:46Z","timestamp":1790693866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/RCM\/27\/9\/10.31083\/RCM51541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":123,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026]]}},"alternative-id":["S2153-8174(26)04643-0"],"URL":"https:\/\/doi.org\/10.31083\/rcm51541","relation":{},"ISSN":["1530-6550","2153-8174"],"issn-type":[{"value":"1530-6550","type":"print"},{"value":"2153-8174","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"article-number":"51541"}}