Bioinspired therapeutic platform based on extracellular vesicles for prevention of arterial wall remodeling in hypertension

Arterial stiffness due to the vessel remodeling is closely linked to raised blood pressure,and its physiopathologic mechanism is still not fully understood.We here aimed to explore whether extracellular vesicle(EV)mediated intercellular communication between endothelium and smooth muscle cell contribute to the blood vessel remodeling under hypertension.We here revealed that the arterial endothelial cells robustly secreted EV,which in turn could be circulated and/or directly taken up by the subendothelial smooth muscle cells(SMC).Under hypertension,the EV secretion increased and the miRNA profile changed significantly mainly due to the raised mechanical force and subsequent enhanced reactive oxygen species generation.Among the miRNA cargos in the EV,miR-320d/423-5p were found increased most significantly.In vivo delivery of miR-320d/423-5p mimics via engineered EV increased their expression in arterial vessels,recapitulating the phenotype in hypertension.In contrast,therapeutic delivery of miR-320d/423-5p inhibitors via engineered EV alleviated the phenotype in spontaneous hypertension rat model.Together,we have found that the injured endothelium due to the raised mechanical force in hypertension contributes to the arterial wall remodeling via the secreted EV.Our study has not only provided novel insights on the mechanism of hypertension associated blood vessel wall remodeling,but also shed light on therapeutic intervention of hypertension associated vascular diseases.

Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal:A nationwide,multicenter study

Background:Carotid intima-media thickness(IMT)and diameter,stiffness,and wave reflections,are independent and important clinical biomarkers and risk predictors for cardiovascular diseases.The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods:A total of 3053 healthy Han Chinese adults(1922 women)aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022.The real-time tracking of common carotid artery walls was achieved by the radio frequency(RF)ultrasound system.The IMT,diameter,compliance coefficient,βstiffness,local pulse wave velocity(PWV),local systolic blood pressure,augmented pressure(AP),and augmentation index(AIx)were then automatically measured and reported.Data were stratified by age groups and sex.The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions.The major clinical determinants of carotid properties were identified by Pearson’s correlation,multiple linear regression,and analyses of covariance.Results:All the parameters of carotid properties demonstrated significantly age-related trajectories.Women showed thinner IMT,smaller carotid diameter,larger AP,and AIx than men.Theβstiffness and PWV were significantly higher in men than women before forties,but the differences reversed after that.The increase rate of carotid IMT(5.5µm/year in women and 5.8µm/year in men)and diameter(0.03 mm/year in both men and women)were similar between men and women.For the stiffness and wave reflections,women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes(all P for age by sex interaction<0.05).The blood pressures,body mass index(BMI),and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex.Conclusions:The age-and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established.The blood pressures,BMI,and triglyceride levels should be considered for clinical application of corresponding reference values.