Human-based evidence for the therapeutic potential of arginase inhibitors in cardiovascular diseases

Arginase is a ubiquitous enzyme that regulates polyamine-and nitric-oxide-requiring vascular functions. It is well-established that, in mammals, arginase overactivation contributes to endothelial dysfunction, a hallmark of cardiovascular diseases. The pharmacological potential of arginase inhibition for improving vascular function is largely supported by a wide range of data from animal studies. However, caution is required before extrapolating animal data to humans because interspecies differences in arginase expression and localization have been observed. For this reason, this review presents the existing arguments from human data in favor of a role of arginase in cardiovascular diseases. Then, the available data from clinical studies are discussed, as well as the possible arginase inhibitors that might be used in future large-scale clinical trials. Cardiovascular diseases (CVDs) are some of the leading causes of mortality and morbidity worldwide. They include conditions such as hypertension, coronary artery disease (CAD), stroke, myocardial ischemia, heart failure and erectile dysfunction, in which atherosclerosis has a pivotal pathological role. The vascular endothelium is a single-layered, continuous cell sheet that lines the luminal vessel wall. It is localized into the intima of vessels between blood and surrounding tissues, including vascular smooth cells in the media [1,2]. More than just a simple mechanical