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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BackgroundThe development of peripheral arterial disease (PAD) is heterogeneous even in the presence of similar risk factors. Our aim was to determine whether inter-individual differences in leukocyte telomere length contribute to the susceptibility of PAD.MethodsA total of 485 patients with PAD (defined by the ankle-brachial index) and 970 age- and gender-matched controls were recruited from seven rural communities in Henan Province in China. The relative leukocyte telomere length was determined by a quantitative PCR-based method. Two common promoter variants of the hTERT gene were genotyped to assess their effects on telomere length and the risk of PAD. In vivo luciferase assay was performed to study the transcriptional activity.ResultsAfter adjustment for vascular risk factors and genetic variants in the hTERT gene, individuals in the lowest and middle tertiles of telomere length had a significantly higher risk of PAD than did those in the highest tertile (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.29–2.49 in the middle tertile; 3.15, 95%CI 2.31–4.29 in the lowest tertile). Haplotype analysis using the 2 variants (rs2735940 and rs2853669) showed that subjects with the at-risk C-C haplotype had shorter telomere length than those individuals with the T-T haplotype and consistently had 1.30-fold (OR 1.30, 95%CI 1.06–1.58; P = 0.005) increased risk for PAD. The C-C haplotype had 43% lowered transcription activity of hTERT promoter (P<0.001).ConclusionThe associations between the functional haplotype of hTERT gene and telomere length and the risk of atherosclerotic PAD suggested that mean leukocyte telomere length may independently serve as a potential predictor of PAD.

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.

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Objective: To identify novel and confirm previously reported metabolites associated with SBP, DBP, and hypertension in a biracial sample of Bogalusa Heart Study (BHS) participants. Methods: We employed untargeted, ultra-high performance liquid chromatography tandem mass spectroscopy metabolomics profiling among 1249 BHS participants (427 African-Americans and 822 whites) with BP and covariable data collected during the 2013 to 2016 visit cycle. A total of 1202 metabolites were tested for associations with continuous and binary BP phenotypes using multiple linear and logistic regression models, respectively, in overall and race-stratified analyses. Results: A total of 24 novel metabolites robustly associated with BP, achieving Bonferroni-corrected P less than 4.16 × 10−5 in the overall analysis and consistent effect sizes across race groups. The identified metabolites included three amino acid and nucleotide metabolites from histidine, pyrimidine, or tryptophan metabolism sub-pathways, seven cofactor and vitamin or xenobiotic metabolites from the ascorbate and aldarate metabolism, bacterial/fungal, chemical, and food component sub-pathways, 10 lipid metabolites from the eicosanoid, phosphatidylcholine, phosphatidylethanolamine, and sphingolipid metabolism sub-pathways, and four still unnamed metabolites. Six previously described metabolites were robustly confirmed by our study (Bonferroni-corrected P < 4.95 × 10−4 and consistent effect directions across studies). Furthermore, previously reported metabolites for SBP, DBP, and hypertension demonstrated 5.92-fold, 4.77-fold, and 4.54-fold enrichment for nominally significant signals in the BHS (P = 3.08 × 10−10, 5.93 × 10−8, and 2.30 × 10−8, respectively). Conclusion: In aggregate, our study provides new information about potential molecular mechanisms underlying BP regulation. We also demonstrate reproducibility of findings across studies despite differences in study populations and metabolite profiling methods.