Egg White-Derived Antihypertensive Peptide IRW (Ile-Arg-Trp) Inhibits Angiotensin II-Stimulated Migration of Vascular Smooth Muscle Cells via Angiotensin Type I Receptor

Excessive proliferation, inflammation, oxidative stress, and migration induced by angiotensin II (Ang II), occurring in vascular smooth muscle cells (VSMCs) during vascular remodelling, are major pathogenesis of hypertension. Antihypertensive peptides derived from food proteins are promising alternatives in preventing/treating hypertension and associated complications. In addition to reducing high blood pressure in spontaneously hypertensive rats, egg white ovotransferrin-derived antihypertensive IRW (Ile-Arg-Trp) was shown to exert antiproliferative, antioxidant, and anti-inflammatory effects in A7r5 cells (a vascular smooth muscle cell line) against Ang II stimulation, further indicating its potential in retarding vascular remodelling. Since its regulatory role in migration of VSMC is unclear, the objective of this study was to evaluate the antimigrant activity of IRW in Ang II-stimulated A7r5 cells. It was found that IRW could downregulate matrix metallopeptidase 9 (MMP9) expression and inhibit migration of Ang II-stimulated A7r5 cells, which was associated with inactivation of p38/MAPK signaling. More importantly, the antimigrant activity of IRW in Ang II-stimulated A7r5 cells was dependent on angiotensin type I receptor (ATTR). Our study provided the first evidence that egg ovotransferrin-derived antihypertensive peptide IRW inhibited migration of VSMCs.