Molecular and biochemical aspects of Homocysteine in Cardiovascular Diseases
Keywords:Metabolic disorders, Homocysteine, Renal dysfunction, methylenetetrahydrofolate reductase, folic acid.
Markedly or mildly elevated circulating homocysteine concentrations are associated with increased risk of vascular occlusion. Here we review possible mechanisms that mediate these effects. Inborn errors of homocysteine metabolism result in markedly elevated plasma homocysteine (200–300 μmol/L) and thromboembolic (mainly venous) disease which is easily normalized with oral folate and ongoing trials are assessing the effect of folate treatment on outcomes. Some people have a common genetic variant (called methylenetetrahydrofolate reductase, abbreviated MTHFR) that also impairs their ability to process folate. Indeed, there are evidences suggesting an acute antioxidant effect of folic acid on homocysteine concentrations. This antioxidant mechanism may oppose an oxidant effect of homocysteine and be relevant to treatment of patients with vascular disease, especially those with chronic renal insufficiency. Such patients have moderately elevated plasma homocysteine and greatly increased cardiovascular risk that is largely unexplained.
Stamler R. The primary prevention of hypertension and the population blood pressure problem. In coronary heart disease epidemiology. Eds: Marmot MG, Elliot P. Oxford. Oxford University Press: 1992; 415-434.
Gupta R, Al-odat NA, Gupta VP. Hypertension epidemiology in India. Meta analysis of fifty-year prevalence rates and blood pressure trends. J Human Hypertension 1996; 10: 465-472.
Gupta R. Trends in hypertension epidemiology in India. J Human Hypertension 2004; 18: 73-78. DOI: 10.1038/sj.jhh.1001633
Refsum H, Nurky EA, Smith D, Ueland PM, Gjesdal CG., Bjelland I, et al. The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease. J Nutr 2006; 136: 1731S-1740S.
Venes D, Clarence WT. In: Taber’s Cyclopedic Medical Dictionary. 1st ed. Venes D, editor. Philadelphia: F.A. Davis; 2005: p.1089. DOI: 10.1016/s0001-2092(07)64922-9
Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet. 1999; 354: 407-413. DOI: 10.1016/s0140-6736(98)11058-9
Loscalzo J, Handy DE. Epigenetic modifications: basic mechanisms and role in cardiovascular disease (2013 Grover Conference Series). Pulm Circ. 2014; 4(2): 169-174. DOI: 10.1086/675979
Harvey RA, Ferrier DR. In: Lippincott’s Illustrated Reviews, Biochemistry. 5thed. Rhyner S, editor. Philadelphia: Wolters Kluwer Health; 2011: 26-45.
Faeh D, Chiolero A, Paccaud F. Homocysteine as a risk factor for cardiovascular disease: should we (still) worry about it? Swiss Med Wkly. 2006;136:745-756.
Guo H, Chi J, Xing Y, Wang P. Influence of folic acid on plasma homocysteine levels & arterial endothelial function in patients with unstable angina. Indian J Med Res. 2009; 129(3): 279-284.
Baszczuk A, Kopczynski Z. Hyperhomocysteinemia in patients with cardiovascular disease. Postepy Hig Med Dosw. 2014; 68: 579-589. DOI: 10.5604/17322693.1102340
Herrmann W. The importance of hyperhomocysteinemia as a risk factor for diseases: an overview. Clin Chem Lab Med. 2001; 39(8):666-74. DOI: 10.1515/cclm.2001.110
Lim U, Cassano PA. Homocysteine and blood pressure in the Third National Health and Nutrition Examination Survey, 1988-1994. Am J Epidemiol 2002; 156: 1105-1113. DOI: 10.1093/aje/kwf157
Maria CP Franco, Elisa MS Higa, Vânia D’Almeida et al. Homocysteine and Nitric Oxide Are Related to Blood Pressure and Vascular Function in Small-for-Gestational-Age Children. Hypertension 2007; 50: 396-400. DOI: 10.1161/hypertensionaha.107.091223
Yajnik CS, Deshpande SS, Panchanadikar AV et al. Maternal total homocysteine concentration and neonatal size in India. Asia Pac J Clin Nutr 2005; 14: 179-181.
Engel SM, Olshan AF, Siega-Riz AM et al. Polymorphisms in folate metabolising genes and risk for spontaneous preterm and smallfor- gestational age birth. Am J Obstet Gynecol 2006; 195: 1-11. DOI: 10.1016/j.ajog.2006.07.024
Lin TK, Liou WS. The concept of B vitamins in prevention of cardiovascular diseases. J Med Sci 2002; 22 (6): 273-276.
Neki NS. Hyperhomocysteinaemia – An independent Risk factor for Cardiovascular diseases. JIACM 2005; 4, 55-60.
Graham IM. Plasma homocysteine as a risk factor for vascular disease.. JAMA 1997; 277: 1775-1781. DOI: 10.1001/jama.1997.03540460039030
Pierdomenico SD, Bucci A, Lapenna D et al. Circulating homocysteine levels in sustaned and white coat hypertension. J Hum Hypertens 2003; 17: 165-170. DOI: 10.1038/sj.jhh.1001524
Rolland PH, Friggi A, Barlatier A et al. Hyperhomocysteinaemiainduced vascular damage in the minipig captopril hydrochlorothiazide combination prevents elastic alterations. Circulation 1995; 91: 1161-1174.
Van Dijk RAJM, Rauwerda JA, Steyn M et al. Long-term homocysteine-lowering treatment with folic acid plus pyridoxine is associated with decreased blood pressure but not with improved brachial artery endothelium-dependent vasodilation or carotid artery stiffness: a 2-year, randomised, placebo-controlled trial. Arterioscler Thromb Vasc Bio 2001; 21: 2072-2079. DOI: 10.1161/hq1201.100223
Van Guldener C, Nanayakkara PW, Stehouwer CD. Homocysteine and blood pressure. Curr Hypertens Re 2003; 5: 26-31. DOI: 10.1007/s11906-003-0007-z
Hackam DG, Anand SS. Emerging risk factors for atherosclerotic vascular disease. JAMA 2003; 290: 932–940. DOI: 10.1001/jama.290.7.932
Chen X, Wang L, Fazlieva R, Kruger WD. Contrasting behaviors of mutant cystathionine beta-synthase enzymes associated with pyridoxine response. Hum Mutat. 2006; 27: 474–482. DOI: 10.1002/humu.20320
Linnebank M, Janosik M, Kozich V, Pronicka E, Kubalska J, Sokolova J, Linnebank A, Schmidt E, Leyendecker C, Klockgether T, Kraus JP, Koch HG. The cystathionine beta-synthase (CBS) mutation c.1224-2A>C in Central Europe: Vitamin B6 nonresponsiveness and a common ancestral haplotype. Hum Mutat. 2004; 24: 352–353. DOI: 10.1002/humu.9280
Lehmann M, Regland B, Blennow K, Gottfries CG. Vitamin B12-B6-folate treatment improves blood-brain barrier function in patients with hyperhomocysteinaemia and mild cognitive impairment. Dement Geriatr Cogn Disord. 2003; 16(3):145-150. DOI: 10.1159/000071002
Shewan LG, Coats AJS, Henein M. Requirements for ethical publishing in biomedical journals. International Cardiovascular Forum Journal 2015;2:2 DOI: 10.17987/icfj.v2i1.4
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