Hyperhomocysteinemia and Alcoholism: A Double Hit?

Hyperhomocysteinemia and Alcoholism: A Double Hit?

Homocysteine (HCY) is a non-protein sulfur-containing amino acid. It has received a great deal of attention over the last two decades within the scientific community for its unique role in the induction of several diseases ranging from atherosclerotic cardiovascular disease to neural tube defects (NTD).  In 1976, the initial epidemiological study of Wilcken and Wilcken 2 supported this hypothesis and provided the first evidence of the pathogenic role of HCY in atherosclerotic cardiovascular disease and alcoholism.

However, in the pathogenic conditions, a selective increase in cell proliferation induces hyperplasia and a selective elevation of apoptosis leads to atrophy. As early as 1973, Ross and Glomset5
proposed that proliferation of smooth muscle cells within the wall of the artery was the key event in the genesis of the lesions of atherosclerosis. Atherosclerosis is a multifactorial process including endothelial dysfunction, and vascular smooth muscle cells (VSMCs) apoptosis, proliferation and migration from the media to the intima, and subsequently, formation of the atherosclerotic plaques. Indeed, apoptosis and proliferation of VSMCs are the most prominent hallmarks of atherosclerotic plaque instability. A stable atherosclerotic plaque possesses a thick fibrous cap with excessive numbers of VSMCs, whereas unstable atherosclerotic plaques have a thin fibrous cap with limited numbers of VSMCs.

To explain these phenomena, one possibility considered is that HCY initiates monocyte, T-lymphocyte, endothelial cell and VSMCs activities that interact with other inflammatory stimuli, sensitize the inflammatory responsiveness leading to an enhanced production of reactive oxygen species (ROS) and a chronic inflammatory condition at the site of atherosclerotic lesions.

Toxicol Forensic Med Open J. 2017; 2(2): 84-87. doi: 10.17140/TFMOJ-2-123