Pathological cardiovascular events including hypertension account for nearly one-third of annual deaths worldwide. Besides standard pharmacological treatment, nutritional intervention via dietary peptides is now recognized as a promising prevention and treatment approach. One of such drug candidates, IRW, a short egg-derived peptide lowers blood pressure and activates angiotensin converting enzyme 2 (ACE 2) <i>in vivo</i>. However, the detailed mechanism of action remains obscure. Our preliminary experiments using smooth aortic muscle cells (a7r5) show that IRW activates nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) via direct interaction with its co-activator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). These targets are known for vasodilation, metabolism and vasculature altering abilities. Further, IRW interacts with heat shock protein 90 (HSP90), a nitric oxide activator, and a detoxifying antioxidant enzyme glutathione S-transferase-1 (GST1). Docking studies are underway for an elucidation of structural mechanisms of these interactions. Also, using spontaneously hypertensive rats, we are studying the interaction of IRW with the suggested pathway <i>in vivo</i>. Tissues with high oxidative capacity, such as heart, aorta, and liver remain on our focus for the elucidation of the pharmacological mechanism of action. Currently, our study presents the first evidence of direct interaction of a short peptide with the therapeutic PGC-1α pathway. This study opens doors for further investigation of IRW in treatment of obesity, atherosclerosis and other metabolic disorders. Further data will be included during presentation at the conference venue.

Short dietary peptide IRW elicits its pharmacological effects via PGC1α axis

255th National Meeting (2018)

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