Korean J Anesthesiol.  2011 Jul;61(1):3-11. 10.4097/kjae.2011.61.1.3.

Endothelial arginase II and atherosclerosis

Affiliations
  • 1Division of Biology, Kangwon National University, Chuncheon, Korea.
  • 2Department of Anesthesiology and Critical Medicine and Biomedical Engineering, The Johns Hopkins Medical Institutes, Baltimore, MD, USA.
  • 3Department of Anesthesiology and Pain Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea. hyunkyolim@yonsei.ac.kr

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.

Keyword

Arginase; Atherosclerosis; Endothelial dysfunction; Endothelial nitric oxide synthase; Vascular smooth muscle cell

MeSH Terms

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
Arginase
Arginine
Collagen
Lipoproteins
Lipoproteins, LDL
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type III
Reactive Oxygen Species
Superoxides
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