In this study, a sulfated polysaccharide (BFP) was isolated from the edible red alga Bangia fusco-purpurea. Gel-filtration and thin layer chromatographically analyses suggested that BFP was a homogenous polysaccharide. The chemical structural analysis revealed that BFP mainly consisted of galactose together with a small amount of uronic acid, mannose, and glucose. Its molecular mass was estimated to be 133.18 kDa by high-performance liquid chromatography (HPLC) analysis. BFP inhibited α-amylase and α-glucosidase in a concentration-dependent manner. The IC50 values of BFP against α-amylase and α-glucosidase were estimated to be 1.26 ± 0.11 mg/mL and 1.34 ± 0.07 mg/mL, respectively. Kinetic analyses suggested that BFP showed competitive and non-competitive inhibition against α-amylase and α-glucosidase, respectively. Circular dichroism spectral and fluorescence spectral analyses suggested that BFP affects the conformational structures of these enzymes, which may lead to the inhibition of the enzymatic activities. Abbreviations: Ara: D-arabinose; AnGal: anhydro-L-galactose residues; CD spectroscopy: Circular Dichroism spectroscopy; DNS: dinitrosalicylic acid; FT-IR: fourier transform infrared spectra; Fuc: L-fucose; Gal: D-galactose; Glc: D-glucose; GlcA: D-Glucuronic acid; HPLC: high performance liquid chromatography; Man: D-mannose; pNPG: p-nitrophenyl-α-D-glucoside; TFA: trifluoroacetic acid; TLC: thin-layer chromatography; PMP: 1-phenyl-3-methyl-5-pyrazolone; Xyl: D-xylose

Endothelial dysfunction is a common disorder of vascular homeostasis in hypertension characterized by oxidative stress, malignant migration, inflammatory response, and active adhesion response of endothelial cells. The extracellular vesicles (EVs), a vital participant in vascular cell communication, have been considered responsible for vascular disease progression. However, the potential mechanism of antihypertensive peptides against the EVs-induced endothelial dysfunction is still unclear. In this study, we investigated whether the antihypertensive peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) ameliorate the effects of EVs from Ang II-induced vascular smooth muscles (VSMCs) on the endothelial dysfunction. The dihydroethidium staining, wound healing assay, 3D cell culture, and co-culture with U937 monocyte were used to investigate the oxidant/antioxidant balance, migration, tube formation, and cell adhesion in EV-induced human umbilical vein endothelial cells. VPP and IPP treatment reduced the level of reactive oxygen species and EV-induced expression of adhesion molecules and restored the ability of tube formation by upregulating endothelial nitric oxide synthase expression. VPP and IPP reduced the protein levels of IL-6 to 227.34 ± 10.56 and 273.84 ± 22.28 pg/mL, of IL-1β protein to 131.56 ± 23.18 and 221.14 ± 13.8 pg/mL, and of MCP-1 to 301.48 ± 19.75 and 428.68 ± 9.59 pg/mL. These results suggested that the VPP and IPP are potential agents that can improve the endothelial dysfunction caused by EVs from Ang II-induced VSMCs.

Angiotensin II (Ang II), a vasoactive factor in the renin−angiotensin−aldosterone system (RAAS), can regulate vasoconstriction and promote multiple vascular diseases. In this study, the effects of potent antihypertensive peptide Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) on the proliferation and migration of vascular smooth muscle cells (VSMCs) by extracellular vesicles (EVs) from vascular endothelial cells (VECs) were studied using a cell co-culture model. The VEC-derived EVs were isolated, characterized, and investigated. The present study demonstrated that the EVs from Ang II-induced VECs could promote proliferation, migration, and inflammatory factors (IL-6 increased to 40.75 ± 4.33 pg/mL and IL-1β increased to 28.62 ± 5.42 pg/ mL) generation of VSMCs, VPP and IPP exerted discrepant inhibitory effects on this pathway. The EVs with RNase treatment lost the effects on VSMCs, indicating that the RNAs packed into vesicles may be a critical component. These results implied that VPP and IPP could alleviate Ang II-induced vascular dysfunction by modulating the EV-mediated transmission of RNAs between VECs and VSMCs.

An emerging inference is that vascular cells transfer their biological cargo to recipient cells by secretion of extracellular vesicles (EVs). This study explored the effects of EVs produced from VSMCs with Ang II (EVs-A) or LSW + Ang II on HUVECs. The EVs-A increase ROS production, activate inflammation, and upregulate the expression of adhesion molecules. Among the EVs-A, miR-22, miR-143, miR-144, and miR-155 were significantly downregulated, while VSMCs pre-incubated with LSW could produce improved EVs. RNA sequencing revealed differential expression of genes associated with endothelial dysfunction, including the TNF signaling pathway, NOD-like receptor signaling pathway, NF-κB signaling pathway, and fluid shear stress and atherosclerosis pathway. Finally, we found that LSW could improve endothelial function by repairing the expression of miRNAs in VSMCs. It also suggests a potential mechanism for the injury action of endogenous peptide Ang II and protective effects of exogenous peptide LSW on vascular endothelial cells.

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