Decreased endothelial
nitric oxide (NO) bioavailability as it relates to endothelial dysfunction plays an important role in various cardiovascular disorders, including athero-
sclerosis. Recent research has provided evidence that endothelial dysfunction in
atherosclerosis is not primarily caused by decreased endothelial
NO synthase (eNOS) gene expression, but rather deregulation of eNOS enzymatic activity, which contributes to the increased oxidative stress in
atherosclerosis. Among other mechanisms, the substrate
L-arginine is an important limiting factor for NO production. Emerging evidence demonstrates that
L-arginine is not only converted to NO via eNOS, but also metabolized to
urea and l-
ornithine via
arginase in endothelial cells. Hence,
arginase competes with eNOS for the substrate
L-arginine, resulting in deceased NO production. There are an increasing number of studies showing that enhanced
arginase gene expression and/or activity contribute to endothelial dysfunction in various cardiovascular disorders, including
atherosclerosis. Thus, endothelial
arginase may represent a new therapeutic target in
atherosclerosis.