Endothelial arginase II and atherosclerosis.
- Author:
Sungwoo RYOO
1
;
Dan E BERKOWITZ
;
Hyun Kyo LIM
Author Information
- Publication Type:Review
- Keywords: Arginase; Atherosclerosis; Endothelial dysfunction; Endothelial nitric oxide synthase; Vascular smooth muscle cell
- MeSH: Animals; Apoptosis; Arginase; Arginine; Atherosclerosis; Cell Proliferation; Collagen; Developed Countries; Endothelial Cells; Lipoproteins; Lipoproteins, LDL; Mice; Muscle, Smooth, Vascular; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Plaque, Atherosclerotic; Reactive Oxygen Species; Superoxides; Vascular Diseases; Vascular Stiffness
- From:Korean Journal of Anesthesiology 2011;61(1):3-11
- CountryRepublic of Korea
- Language:English
- Abstract: Atherosclerotic vascular disease is the leading cause of morbidity and mortality in developed countries. While it is a complex condition resulting from numerous genetic and environmental factors, it is well recognized that oxidized low-density lipoprotein produces pro-atherogenic effects in endothelial cells (ECs) by inducing the expression of adhesion molecules, stimulating EC apoptosis, inducing superoxide anion formation and impairing protective endothelial nitric oxide (NO) formation. Emerging evidence suggests that the enzyme arginase reciprocally regulates NO synthase and NO production by competing for the common substrate L-arginine. As oxidized LDL (OxLDL) results in arginase activation/upregulation, it appears to be an important contributor to endothelial dysfunction by a mechanism that involves substrate limitation for endothelial NO synthase (eNOS) and NO synthesis. Additionally, arginase enhances production of reactive oxygen species by eNOS. Arginase inhibition in hypercholesterolemic (ApoE-/-) mice or arginase II deletion (ArgII-/-) mice restores endothelial vasorelaxant function, reduces vascular stiffness and markedly reduces atherosclerotic plaque burden. Furthermore, arginase activation contributes to vascular changes including polyamine-dependent vascular smooth muscle cell proliferation and collagen synthesis. Collectively, arginase may play a key role in the prevention and treatment of atherosclerotic vascular disease.
