Hyperhomocysteinemia and cardiovascular disease: new mechanisms beyond atherosclerosis.
The association of hyperhomocysteinemia (Hhe) with cardiovascular disease (CVD) has been explored in detail over the last four decades since initial reports in the 1960s. Although several epidemiological studies have shown an association, convincing mechanistic studies are still lacking. However, recent prospective studies demonstrate a strong association of Hhe with coronary disease. Several pathogenic mechanisms have been studied in Hhe and indicate alterations in the various components of vascular disease, namely endothelial cells, vascular smooth muscle cells, platelets, and the coagulation/fibrinolytic systems. Increased oxidative stress, hypomethylation, and protein homocysteinylation have been proposed as potential molecular mechanisms in Hhe-induced CVD. In addition, recent studies indicate a novel link between Hhe and CVD, that is, direct effects on coronary arteriolar and myocardial remodeling resulting in cardiac dysfunction.
Joseph
Jacob
J
The Departments of Internal Medicine and Pharmaceutical Sciences, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas.
Joseph
Lija
L