Vascular Oxidant Stress and Inflammation in Hyperhomocysteinemia

Abstract

Elevated plasma levels of homocysteine are a metabolic risk factor for atherosclerotic vascular disease, as shown in numerous clinical studies that linked elevated homocysteine levels to de novo and recurrent cardiovascular events. High levels of homocysteine promote oxidant stress in vascular cells and tissue because of the formation of reactive oxygen species (ROS), which have been strongly implicated in the development of atherosclerosis. In particular, ROS have been shown to cause endothelial injury, dysfunction, and activation. Elevated homocysteine stimulates proinflammatory pathways in vascular cells, resulting in leukocyte recruitment to the vessel wall, mediated by the expression of adhesion molecules on endothelial cells and circulating monocytes and neutrophils, in the infiltration of leukocytes into the arterial wall mediated by increased secretion of chemokines, and in the differentiation of monocytes into cholesterol-scavenging macrophages. Furthermore, it stimulates the proliferation of vascular smooth muscle cells followed by the production of extracellular matrix. Many of these events involve redox-sensitive signaling events, which are promoted by elevated homocysteine, and result in the formation of atherosclerotic lesions. In this article, we review current knowledge about the role of homocysteine on oxidant stress-mediated vascular inflammation during the development of atherosclerosis.

Decreased Serum Paraoxonase 1 Activity and Increased Serum Homocysteine and Malondialdehyde Levels in Age-Related Macular Degeneration

“…However, the exact mechanism of the damage is unknown (Hankey and Eikelboom 1999). Toxic hydrogen peroxide and hydroxyl radicals are generated during the autooxidation of homocysteine, and these radicals promote oxidative stress (Papatheodorou and Weiss 2007). In experimental studies, various possible mechanisms have been proposed to account for the vascular effects of homocysteine.…”

Novel Role of NOD2 in Mediating Ca 2+ Signaling

“…An elevated level of Hcys has been demonstrated to induce chronic inflammation in the vascular bed, including glomerulus. 13,14 However, it remains unknown whether NOD2-mediated signaling in renal glomerular residential cells contributes to the pathogenesis of renal injury in hHcys.…”

Synergistic Association of Serum Albumin and Globulin with Coronary Heart Disease

“…Indirect antioxidant activity of albumin comes from its ability to bind and transport bilirubin, which has been shown to act as an inhibitor of lipid peroxidation 29) . Albumin also can bind homocysteine, resulting in a decreased level of serum homocysteine, which is a risk factor for atherosclerosis 30) . The results of basic scientific research suggest that globulins contain anti-atherosclerotic components (e.g., γ-globulin).…”