Ameliorated biomechanical properties of carotid arteries by puerarin in spontaneously hypertensive rats.

BACKGROUND: An emerging body of evidence indicates that puerarin (PUE) plays an important role in the treatment of angina pectoris, myocardial ischemia-reperfusion injury, hypertension and other cardiovascular diseases, but how PUE affects the vascular remodeling of hypertensive rats has not been reported yet. This study aimed to investigate the effect and mechanism of PUE on carotid arteries of spontaneously hypertensive rats (SHR) to provide the basis for the clinical application of PUE. METHODS: Thirty male SHR and six male Wistar Kyoto rats (WKY) aged 3 months were used in this study, SHR rats were randomly divided into 5 groups, PUE(40 or 80 mg/kg/d, ip) and telmisartan (TELMI) (30 mg/kg/d, ig) were administrated for 3 months. We use DMT myography pressure-diameter system to investigate biomechanical properties of carotid arteries, 10 µM pan-classical transient receptor potential channels (TRPCs) inhibitor SKF96365, 200 nM specific TRPC6 inhibitor SAR7334 and 100 µM Orai1 inhibitor ANCOA4 were used in the mechanical test. RESULTS: PUE can significantly decrease systolic and diastolic blood pressure, long-term administration of PUE resulted in a mild reduction of thickness and inner diameter of carotid artery. PUE ameliorate NE-response and vascular remodeling mainly through inhibiting TRPCs channel activities of VSMC. CONCLUSION: PUE can ameliorate biomechanical remodeling of carotid arteries through inhibiting TRPCs channel activities of VSMC in spontaneously hypertensive rats.

Bone marrow mesenchymal stem cells-derived extracellular vesicles carrying microRNA-221-3p protect against ischemic stroke via ATF3.

OBJECTIVE: We aim to explore the protective effect of bone marrow mesenchymal stem cells (BMSCs)-derived exosomal microRNA-221-3p (miR-221-3p) on ischemic stroke (IS) by targeting activating transcription factor 3 (ATF3). METHODS: The middle cerebral artery occlusion (MCAO) mice model and oxygen-glucose deprivation (OGD) neuron model were established. Extracellular vesicles were isolated from BMSCs (BMSC-EVs) and transfected with altered miR-221-3p or ATF3 to treat the MCAO mice and OGD-treated neurons. MiR-221-3p and ATF3 expression were determined, and the contents of inflammatory factors were detected. The pathological changes and apoptosis in mice brain tissues were observed. In cellular experiments, the viability and apoptosis of OGD-treated neurons were evaluated. Binding relationship between miR-221-3p and ATF3 was determined. RESULTS: MiR-221-3p was down-regulated and ATF3 was up-regulated in MCAO mice and OGD-treated neurons. BMSC-EVs and BMSC-EVs carrying up-regulated miR-221-3p attenuated inflammation, pathological changes and apoptosis in MCAO mice brain tissues, and also promoted viability and repressed apoptosis of OGD-treated neurons. ATF3 was verified as a target of miR-221-3p. CONCLUSION: BMSC-EVs carrying miR-221-3p protect against IS by inhibiting ATF3. This study may be helpful for exploring therapeutic strategies of IS.