{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:16:54Z","timestamp":1793377014764,"version":"4.5.0"},"reference-count":155,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J Angiol"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Ischemic stroke and heart disease, coronary heart disease, and cardiovascular disease are events resulting from long-lasting and silent atherosclerosis. This paper deals with the synthesis of homocysteine (Hcy), causes of HHcy, mechanism of HHcy-induced atherosclerosis, and treatment of HHcy. Synthesis and metabolism of Hcy involves demethylation, transmethylation, and transsulfuration, and these processes require vitamin B6 and vitamin B12 folic acid (vitamin B9). Causes of HHcy include deficiency of vitamins B6, B9, and B12, genetic defects, use of smokeless tobacco, cigarette smoking, alcohol consumption, diabetes, rheumatoid arthritis, low thyroid hormone, consumption of caffeine, folic acid antagonist, cholesterol-lowering drugs (niacin), folic acid antagonist (phenytoin), prolonged use of proton pump inhibitors, metformin, and hypertension. HHcy-induced atherosclerosis may be mediated through oxidative stress, decreased availability of nitric oxide (NO), increased expression of monocyte chemoattractant protein-1, smooth muscle cell proliferation, increased thrombogenicity, and induction of arterial connective tissue. HHcy increases the generation of atherogenic biomolecules such as nuclear factor-kappa B, proinflammatory cytokines (IL-1\u03b2, IL-6, and IL-8), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selection), growth factors (IGF-1 and TGF-\u03b2), and monocyte colony-stimulating factor which lead to the development of atherosclerosis. NO which is protective against the development of atherosclerosis is reduced by HHcy. Therapy with folic acid, vitamin B6, and vitamin B12 lowers the levels of Hcy, with folic acid being the most effective. Dietary sources of folic acid, vitamin B6, vitamin B12, omega-3 fatty acid, and green coffee extract reduce Hcy. Abstaining from drinking coffee and alcohol, and smoking also reduces blood levels of Hcy. In conclusion, HHcy induces atherosclerosis by generating atherogenic biomolecules, and treatment of atherosclerosis-induced diseases may be by reducing the levels of Hcy.<\/jats:p>","DOI":"10.1055\/s-0044-1788280","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T22:55:28Z","timestamp":1720479328000},"page":"262-270","source":"Crossref","is-referenced-by-count":13,"title":["Atherogenic Effect of Homocysteine, a Biomarker of Inflammation and Its Treatment"],"prefix":"10.1055","volume":"33","author":[{"given":"Kailash","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3389\/fnins.2016.00538","article-title":"Role of homocysteine in the ischemic stroke and development of ischemic tolerance","volume":"10","author":"J Lehotsk\u00fd","year":"2016","journal-title":"Front Neurosci"},{"issue":"03","key":"ref2","doi-asserted-by":"crossref","first-page":"e420","DOI":"10.1055\/s-0041-1735978","article-title":"Hyperhomocysteinemia and ischemic stroke: a potential dose-response association\u2014a systematic review and meta-analysis","volume":"5","author":"M Holmen","year":"2021","journal-title":"TH Open"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.arr.2018.10.010","article-title":"Homocysteine and age-associated disorders","volume":"49","author":"E A Ostrakhovitch","year":"2019","journal-title":"Ageing Res Rev"},{"issue":"12","key":"ref4","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1161\/01.ATV.18.12.1895","article-title":"Serum homocysteine and risk of coronary heart disease and cerebrovascular disease in elderly men: a 10-year follow-up","volume":"18","author":"C DA Stehouwer","year":"1998","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"03","key":"ref5","doi-asserted-by":"crossref","first-page":"e013934","DOI":"10.1161\/JAHA.119.013934","article-title":"Association between homocysteine and vascular calcification incidence, prevalence, and progression in the MESA cohort","volume":"9","author":"A B Karger","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"ref6","volume-title":"B vitamins, and cardiovascular risk","author":"N G Homocysteine"},{"key":"ref7","first-page":"13","article-title":"Hyperhomocysteinemia: a risk of CVD","volume":"6","author":"N Mishra","year":"2016","journal-title":"Int J Res Biol Sci"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1475-2891-14-6","article-title":"Role of homocysteine in the development of cardiovascular disease","volume":"14","author":"P Ganguly","year":"2015","journal-title":"Nutr J"},{"issue":"11","key":"ref9","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1111\/jch.13073","article-title":"Relationship between homocysteine and hypertension: new data add to the debate","volume":"19","author":"J Skeete","year":"2017","journal-title":"J Clin Hypertens (Greenwich)"},{"issue":"27","key":"ref10","doi-asserted-by":"crossref","first-page":"e16085","DOI":"10.1097\/MD.0000000000016085","article-title":"Association between homocysteine level and blood pressure traits among Tibetans: a cross-sectional study in China","volume":"98","author":"P Sun","year":"2019","journal-title":"Medicine (Baltimore)"},{"issue":"19","key":"ref11","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1001\/jama.1995.03530190040032","article-title":"Total plasma homocysteine and cardiovascular risk profile. 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