The anti-inflammatory effect of vasoactive peptides from soybean protein hydrolysates by mediating serum extracellular vesicles-derived miRNA-19b/CYLD/TRAF6 axis in the vascular microenvironment of SHRs

Abstract

The excessive accumulation of angiotensin II (Ang II) in the vascular microenvironment promotes vascular dysfunction including vascular endothelial inflammation and remodeling. In the present study, a soybean protein hydrolysate enriching with vasoactive peptides was prepared and explored the anti-inflammatory effects on the aorta of spontaneous hypertensive rats (SHRs). The soybean-derived vasoactive peptide (SVP) significantly reduced the blood pressure and attenuated inflammation of the aorta in SHRs. Pathologically, the SVP improved the wall thickening and inflammatory cell infiltration of the aorta. Mechanistically, the SVP not only reduced the expression of miRNA-19b in the aorta but down-regulated the packaging of miRNA-19b in serum EVs. The miRNA-19b targeted the deubiquitinating enzyme cylindromatosis (CYLD) in the aorta and broke the ubiquitination balance of CYLD-TRAF6. These results caused a disorder of the TRAF6-mediated signaling pathway in the aorta, which resulted in upregulation of the expression of IL-6 and TNF-α in the aorta. This pathological process in SHRs was improved by the SVP hydrolysate gavage administration. These results reported a novel anti-inflammatory mechanism of SVP through the serum EVs mediating the miR-19b/CYLD/TRAF6 axis.