Neuropeptide Y: multiple receptors and multiple roles in cardiovascular diseases

Neuropeptide Y (NPY), a sympathetic co-transmitter, acts through multiple G protein-coupled receptors (Y1 to y6) to elicit its vast range of effects in the cardiovascular, immune, and central and peripheral nervous systems. Initially, the focus of the function of NPY in the cardiovascular system involved its acute actions, such as vasoconstriction via the Y1 receptor. However, recent studies have shown that NPY is a potent growth and angiogenic factor, which acts on multiple receptor subtypes. To be more specific, NPY-mediated vascular smooth muscle cell growth, leading to neointima formation, involves Y1 and Y1 receptors, while the angiogenic effects of NPY include Y2 and Y5 receptor activation. The presence of dipeptidyl peptidase IV also influences the cardiovascular responses of NPY by acting as a converting enzyme, shifting NPY activities away from Y1. Thus, agonists and antagonists aimed at the NPY system represent a new avenue for drug treatment, which may help alleviate several cardiovascular disorders in which vascular remodeling plays a major role, such as atherosclerosis, restenosis following balloon angioplasty, hypertension and peripheral vascular disease.