Arginase as a potential target in the treatment of cardiovascular disease: reversal of arginine steal?

被引:237
作者
Pernow, John [1 ]
Jung, Christian [1 ,2 ]
机构
[1] Karolinska Univ Hosp, Karolinska Inst, Cardiol Unit, Dept Med, S-17176 Stockholm, Sweden
[2] Univ Jena, Univ Hosp Jena, Dept Internal Med 1, D-07740 Jena, Germany
基金
瑞典研究理事会;
关键词
Arginase; Nitric oxide; Reactive oxygen species; Atherosclerosis; Ischaemia; Diabetes mellitus; Hypertension; NITRIC-OXIDE SYNTHASE; REFLEX CUTANEOUS VASODILATATION; CORONARY ARTERIOLAR DILATION; ACTIVATED PROTEIN-KINASE; ENDOTHELIAL DYSFUNCTION; VASCULAR DYSFUNCTION; UP-REGULATION; MEDIATED DILATION; PULMONARY-HYPERTENSION; CORPORA CAVERNOSA;
D O I
10.1093/cvr/cvt036
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 ischaemiareperfusion 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.
引用
收藏
页码:334 / 343
页数:10
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