Functions and Mechanisms of Arginase in Age-Associated Cardiovascular Diseases

Abstract

Advanced age is a prominent risk factor of cardiovascular and metabolic diseases, such as atherosclerosis and type II diabetes. The underlying mechanisms are complex and not fully understood. Recent studies provide accumulating evidence demonstrating a potential role of arginases including arginase-I and arginase-II, the isoenzymes involved in L-arginine metabolism, in cardiovascular aging and metabolic diseases by affecting the functions of vascular endothelial cells, smooth muscle cells, and macrophages. At the molecular level, a positive interaction between the arginase II and mTOR-S6K1 pathway has been now demonstrated to play an important role in promoting oxidative stress, inflammation, cellular proliferation, senescence and death, which ultimately leads to accelerated vascular diseases and metabolic disorders. This article reviews the most recent advances in understanding the functional roles and mechanisms of arginase isoforms in cardiovascular aging and the potential of novel therapies to targeting arginases as a means to moderate cardiovascular and metabolic diseases associated with aging.