Small extracellular vesicles from rat plasma promote migration and proliferation of vascular smooth muscle cells.

Small extracellular vesicles (sEV) contain various molecules and mediate cell-to-cell communication under both physiological and pathological conditions. We have recently reported that sEV isolated from plasma of normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) regulate systemic blood pressure. The initiation and development of hypertension partly rely on proliferation and migration of vascular smooth muscle cells (SMCs) followed by the structural remodeling of vascular wall. In the present study, we examined the effects of plasma sEV in WKY and SHR on the proliferative and migratory functions of primary rat aortic SMCs. There was no difference in the concentration and size distribution of plasma sEV between WKY and SHR, while the protein expression of CD81 in plasma sEV from SHR was lower than that from WKY. Both plasma sEV from WKY and SHR were internalized into SMCs and stimulated the migration and proliferation with a similar potency. In summary, we, for the first time, demonstrated that plasma sEV in WKY and SHR are physiologically active in terms of proliferative and migratory functions, however, these effects do not seem to be related to the pathogenesis of hypertension development.

Plasma exosomes regulate systemic blood pressure in rats.

Exosomes, the smallest extracellular vesicle, contain various molecules and mediate cell-cell communication. A number of studies demonstrate exosomes are involved in important physiological and pathological processes. Moreover, microRNA (miRNA) regulating hypertension development through the suppression of certain translation was recently reported. However, roles of exosomes containing various molecules including miRNA on development of essential hypertension have not been examined. We tested the hypothesis that plasma exosomes regulate systemic blood pressure in normotensive and spontaneously hypertensive rats (SHR). Normotensive Wistar Kyoto rats (WKY) and SHR (5-10-week-old) were intraperitoneally administrated with exosomes derived from plasma in WKY or SHR weekly for 6 weeks. Exosomes were isolated by an ultracentrifuge method. SHR-derived exosomes significantly increased systolic blood pressure in WKY, while WKY-derived exosomes decreased it in SHR. In WKY, SHR-derived exosomes induced modest structural changes of thoracic aorta, such as wall thickening and decreased abundance of collagen, which were similar to the changes observed in SHR. On the contrary, WKY-derived exosomes tended to reverse the changes in SHR. WKY-derived exosomes significantly suppressed the increased prostaglandin F2α-induced contraction of mesenteric arterial smooth muscle in SHR. In addition, wet weight and perivascular fibrosis of left ventricles in WKY were significantly increased by SHR-derived exosomes, while the fibrosis but not ventricular weight was significantly decreased by WKY-derived exosomes in SHR. We for the first time demonstrated that plasma exosomes can modulate systemic blood pressure as well as structure and function of cardiovascular tissues in both normotensive and hypertensive rats.