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

The hexapeptide APPLRP from the edible <i>Grifola frondosa</i> mushroom has been verified to possess significant ACE inhibitory activity and ameliorates vascular remodeling. However, <i>in vivo</i> effects have not been systematically investigated. The present study aimed to explore the <i>in vivo</i> 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.