Atherosclerosis and angiogenesis: what do nerves have to do with it?

Area of Science:

• Cardiovascular Biology
• Neuroendocrinology
• Vascular Medicine

Background:

• Neuropeptide Y (NPY) is a neurotransmitter involved in stress, appetite, and vasoconstriction.
• NPY also acts as a growth factor and is angiogenic, suggesting roles in atherosclerosis and tissue repair.
• The dual nature of NPY's effects, termed the "Janus phenomenon," necessitates understanding receptor specificity.

Purpose of the Study:

• To investigate the receptor mechanisms underlying NPY's opposing roles in vascular disease.
• To determine if NPY's pro-atherosclerotic and angiogenic activities can be pharmacologically separated.
• To explore therapeutic strategies targeting specific NPY receptors.

Main Methods:

• Studied NPY receptor expression (Y1-Y5) in relation to angiogenic and pro-atherosclerotic activities.
• Utilized rodent models of limb ischemia and vascular angioplasty.
• Investigated the roles of nitric oxide and dipeptidyl peptidase IV (DPPIV) in NPY signaling.

Main Results:

• Endothelial Y2 receptors mediated NPY's angiogenic effects, while vascular smooth muscle Y1 receptors mediated pro-atherosclerotic effects.
• Limb ischemia upregulated the NPY-Y2 system, promoting revascularization, which was enhanced by exogenous NPY.
• NPY-induced angiogenesis depended on nitric oxide and DPPIV, and was resistant to Y1 blockade; atherosclerosis was mediated by Y1 and blocked by antagonists.

Conclusions:

• NPY's beneficial (angiogenic) and detrimental (atherosclerotic) actions are mediated by distinct receptor pathways (Y2 and Y1, respectively).
• Targeting Y1 receptors with antagonists may treat atherosclerosis and restenosis.
• Targeting Y2 receptors with agonists could promote therapeutic angiogenesis in ischemic conditions.