Antihypertension and Improvement Effects of Hexapeptide APPLRP on Exosomes-Mediated Vascular Endothelial Inflammation in Spontaneously Hypertensive Rats

The hexapeptide APPLRP from the edible Grifola frondosa mushroom has been verified to possess significant ACE inhibitory activity and ameliorates vascular remodeling. However, in vivo effects have not been systematically investigated. The present study aimed to explore the in vivo mechanisms of antihypertensive peptide APPLRP. The APPLRP significantly reduced both systolic and diastolic blood pressure in SHRs and improved disruptions of the renin-angiotensin system in circulation, as evidenced by decreased serum Ang II levels and ACE activity. APPLRP intervention ameliorated the aortic wall thickening and cardiac collagen deposition. APPLRP downregulated miR-125, miR-34a, and miR-150 while restoring the serum exosomal load of miR-145 and miR-143 in SHR. Exosomes from SHR could be captured by HUVECs and induced excessive secretion of inflammatory factors by activating the TLR4-mediated signaling pathway. APPLRP significantly ameliorated SHR-Exos-induced endothelial inflammation by downregulating STAT3, Akt, and p38 phosphorylation.