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Can J Physiol Pharmacol. 2018 Oct;96(10):991-1003. doi: 10.1139/cjpp-2018-0112. Epub 2018 Aug 21.

Homocysteine and homocysteine-related compounds: an overview of the roles in the pathology of the cardiovascular and nervous systems.

Author information

1
a Institute of Medical Physiology "Richard Burian" Faculty of Medicine, University of Belgrade, Visegradska 26, Belgrade 11000, Serbia.
2
b Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia.
3
c Department of Human Pathology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya st. 8, Moscow 119991, Russia.

Abstract

Homocysteine, an amino acid containing a sulfhydryl group, is an intermediate product during metabolism of the amino acids methionine and cysteine. Hyperhomocysteinemia is used as a predictive risk factor for cardiovascular disorders, the stroke progression, screening for inborn errors of methionine metabolism, and as a supplementary test for vitamin B12 deficiency. Two organic systems in which homocysteine has the most harmful effects are the cardiovascular and nervous system. The adverse effects of homocysteine are achieved by the action of several different mechanisms, such as overactivation of N-methyl-d-aspartate receptors, activation of Toll-like receptor 4, disturbance in Ca2+ handling, increased activity of nicotinamide adenine dinucleotide phosphate-oxidase and subsequent increase of production of reactive oxygen species, increased activity of nitric oxide synthase and nitric oxide synthase uncoupling and consequent impairment in nitric oxide and reactive oxygen species synthesis. Increased production of reactive species during hyperhomocysteinemia is related with increased expression of several proinflammatory cytokines, including IL-1β, IL-6, TNF-α, MCP-1, and intracellular adhesion molecule-1. All these mechanisms contribute to the emergence of diseases like atherosclerosis and related complications such as myocardial infarction, stroke, aortic aneurysm, as well as Alzheimer disease and epilepsy. This review provides evidence that supports the causal role for hyperhomocysteinemia in the development of cardiovascular disease and nervous system disorders.

KEYWORDS:

cardiovascular system; homocysteine; homocystéine; hyperexcitability; hyperexcitabilité; hyperhomocysteinemia; hyperhomocystéinémie; nervous system; système cardiovasculaire; système nerveux

PMID:
30130426
DOI:
10.1139/cjpp-2018-0112
[Indexed for MEDLINE]

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