Vascular endothelial senescence contributes to atherosclerosis and coronary artery disease (CAD), but the mechanisms are yet to be clarified. We identified that microRNA‐216a (miR‐216a) significantly increased in senescent endothelial cells. The replicative senescence model of human umbilical vein endothelial cells (HUVECs) was established to explore the role of miR‐216a in endothelial ageing and dysfunction. Luciferase assay indicated that Smad3 was a direct target of miR‐216a. Stable expression of miR‐216a induced a premature senescence‐like phenotype in HUVECs with an impairment in proliferation and migration and led to an increased adhesion to monocytes by inhibiting Smad3 expression and thereafter modulating the degradation of NF‐κB inhibitor alpha (IκBα) and activation of adhesion molecules. Conversely, inhibition of endogenous miR‐216a in senescent HUVECs rescued Smad3 and IκBα expression and inhibited monocytes attachment. Plasma miR‐216a was significantly higher in old CAD patients (>50 years) and associated with increased 31% risk for CAD (odds ratio 1.31, 95% confidence interval 1.03‐1.66; P = .03) compared with the matched healthy controls (>50 years). Taken together, our data suggested that miR‐216a promotes endothelial senescence and inflammation as an endogenous inhibitor of Smad3/IκBα pathway, which might serve as a novel target for ageing‐related atherosclerotic diseases.

The effect of tea intake on blood pressure (BP) is controversial. We performed a meta-analysis of randomised controlled trials to determine the changes in systolic and diastolic BP due to the intake of black and green tea. A systematic search was conducted in MEDLINE, EMBASE and the Cochrane Controlled Trials Register up to May 2014. The weighted mean difference was calculated for net changes in systolic and diastolic BP using fixed-effects or random-effects models. Previously defined subgroup analyses were performed to explore the influence of study characteristics. A total of twenty-five eligible studies with 1476 subjects were selected. The acute intake of tea had no effects on systolic and diastolic BP. However, after long-term tea intake, the pooled mean systolic and diastolic BP were lower by 21·8 (95 % CI 2 2·4, 21·1) and 21·4 (95 % CI 22·2, 2 0·6) mmHg, respectively. When stratified by type of tea, green tea significantly reduced systolic BP by 2·1 (95 % CI 22·9, 2 1·2) mmHg and decreased diastolic BP by 1·7 (95 % CI 22·9, 2 0·5) mmHg, and black tea showed a reduction in systolic BP of 1·4 (95 % CI 22·4, 20·4) mmHg and a decrease in diastolic BP of 1·1 (95 % CI 21·9, 20·2) mmHg. The subgroup analyses showed that the BP-lowering effect was apparent in subjects who consumed tea more than 12 weeks (systolic BP 22·6 (95 % CI 23·5, 21·7) mmHg and diastolic BP 22·2 (95 % CI 2 3·0, 21·3) mmHg, both P,0·001). The present findings suggest that long-term ($12 weeks) ingestion of tea could result in a significant reduction in systolic and diastolic BP.

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Background Diastolic dysfunction is one important causal factor for heart failure with preserved ejection fraction, yet the metabolic signature associated with this subclinical phenotype remains unknown. Methods and Results Ultra‐high‐performance liquid chromatography–tandem mass spectroscopy was used to conduct untargeted metabolomic analysis of fasting serum samples in 1050 white and black participants of the BHS (Bogalusa Heart Study). After quality control, 1202 metabolites were individually tested for association with 5 echocardiographic measures of left ventricular diastolic function using multivariable‐adjusted linear regression. Measures of left ventricular diastolic function included the ratio of peak early filling velocity to peak late filling velocity, ratio of peak early filling velocity to mitral annular velocity, deceleration time, isovolumic relaxation time, and left atrial maximum volume index ( LAVI ). Analyses adjusted for multiple cardiovascular disease risk factors and used Bonferroni‐corrected alpha thresholds. Eight metabolites robustly associated with left ventricular diastolic function in the overall population and demonstrated consistent associations in white and black study participants. N‐formylmethionine (B=0.05; P =1.50×10 −7 ); 1‐methylhistidine (B=0.05; P =1.60×10 −7 ); formiminoglutamate (B=0.07; P =5.60×10 −7 ); N2, N5‐diacetylornithine (B=0.05; P =1.30×10 −7 ); N‐trimethyl 5‐aminovalerate (B=0.04; P =5.10×10 −6 ); 5‐methylthioadenosine (B=0.04; P =1.40×10 −5 ); and methionine sulfoxide (B=0.04; P =3.80×10 −6 ) were significantly associated with the natural log of the ratio of peak early filling velocity to mitral annular velocity. Butyrylcarnitine (B=3.18; P =2.10×10 −6 ) was significantly associated with isovolumic relaxation time. Conclusions The current study identified novel findings of metabolite associations with left ventricular diastolic function, suggesting that the serum metabolome, and its underlying biological pathways, may be implicated in heart failure with preserved ejection fraction pathogenesis.