title: Arginase as a potential target in the treatment of cardiovascular disease: reversal of arginine steal?
abstract: Functional integrity of the vascular endothelium is of fundamental importance for normal vascular function. A key factor regulating endothelial function is the bioavailability of nitric oxide (NO). Recently, the enzyme arginase has emerged as an important regulator of NO production by competing for l-arginine, which is a substrate for both arginase and NO synthase. Increased activity of arginase may reduce the availability of l-arginine for NO synthase, thus reducing NO production, increasing formation of reactive oxygen species, and leading ultimately to endothelial dysfunction. Increased activity and expression of arginase have been demonstrated in several pathological cardiovascular conditions, including hypertension, pulmonary arterial hypertension, atherosclerosis, myocardial ischaemia, congestive heart failure, and vascular dysfunction in diabetes mellitus. Experimental studies have demonstrated that inhibition of arginase under these conditions increases NO bioavailability, reduces oxidative stress, improves vascular function, and protects against ischaemia-reperfusion injury. Initial clinical interventional studies are also promising. The purpose of this review is to discuss the role of arginase in cardiovascular pathologies, its contribution to the development of several cardiovascular disease states and the feasibility of using arginase inhibition as a therapeutic strategy.
authors: Department of Medicine, Cardiology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm 17176, Sweden. john.pernow@ki.se
authors: John
authors: J
authors: Pernow
authors: Christian
authors: C
authors: Jung
mesh_terms: D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D001119:Arginase
keywords: Arginase; Atherosclerosis; Diabetes mellitus; Hypertension; Ischaemia; Nitric oxide; Reactive oxygen species