Shulin Wu

Circular RNAs (circRNAs) participate in regulating gene expression in diverse biological and pathological processes. The present study aimed to investigate the mechanism underlying the modulation of circRNA_000203 on expressions of fibrosis-associated genes in cardiac fibroblasts. CircRNA_000203 was shown upregulated in the diabetic mouse myocardium and in Ang-II-induced mouse cardiac fibroblasts. Enforced-expression of circRNA_000203 could increase expressions of Col1a2, Col3a1 and α-SMA in mouse cardiac fibroblasts. RNA pull-down and RT-qPCR assay indicated that circRNA_000203 could specifically sponge miR-26b-5p. Dual luciferase reporter assay revealed that miR-26b-5p interacted with 3'UTRs of Col1a2 and CTGF, and circ_000203 could block the interactions of miR-26b-5p and 3'UTRs of Col1a2 and CTGF. Transfection of miR-26b-5p could post-transcriptionaly inhibit expressions of Col1a2 and CTGF, accompanied with the suppressions of Col3a1 and α-SMA in cardiac fibroblasts. Additionally, over-expression of circRNA_000203 could eliminate the anti-fibrosis effect of miR-26b-5p in cardiac fibroblasts. Together, our results reveal that suppressing the function of miR-26b-5p contributes to the pro-fibrosis effect of circRNA_000203 in cardiac fibroblasts.

OBJECTIVE: To determine AF prevalence and gaps in atrial fibrillation (AF) awareness and management in China. METHODS: We conducted a community-based survey of 47 841 adults (age ≥45 years) in seven geographic regions of China between 2014 and 2016. Participants underwent a structured questionnaire, a standard 12-lead ECG, physical examination and blood sampling. AF prevalence, defined by either ECG detection or self-report, was estimated according to sampling weights, non-response and age and sex distribution of the population. We used multivariable logistic regression to estimate associations among sociodemographic, clinical and geographic factors with the AF prevalence, awareness and treatment. RESULTS: The weighted AF prevalence was 1.8% (95% CI 1.7% to 1.9%), but varied from 0.9% to 2.4% across geographical regions and equates to being present in an estimated 7.9 (95% CI 7.4 to 8.4) million people in China. Among men and women, the AF prevalence increased from 0.8% and 0.6% in the age group 45-54 years to 5.4% and 4.9% in the age group ≥75 years, respectively. Proportions of people who were aware of having AF decreased overall from 65.3% in 45-54 year-olds to 53.9% in ≥75 year-olds and varied between sex (men 58.5%, women 68.8%) and residency status (urban 78.3%, rural 35.3%). Only 6.0% of patients with high-risk AF received anticoagulation therapy. CONCLUSIONS: AF prevalence is higher than previously reported in China, with low awareness and large treatment gaps. Large-scale efforts are urgently needed to reduce AF adverse consequences.

BACKGROUND: Despite improvements in diagnostic and therapeutic interventions to combat cardiovascular disease (CVD) in recent decades, there are significant ongoing access gaps and sex disparities in prevention that have not been adequately quantified in China. METHODS: A representative, cross-sectional, community-based survey of adults (aged ≥45 years) was conducted in 7 geographic regions of China between 2014 and 2016. Logistic regression models were used to determine sex differences in primary and secondary CVD prevention, and any interaction by age, education level, and area of residence. Data are presented as adjusted odds ratios (ORs) and 95% CIs. RESULTS: Of 47 841 participants (61.3% women), 5454 (57.2% women) had established CVD and 9532 (70.5% women) had a high estimated 10-year CVD risk (≥10%). Only 48.5% and 48.6% of women and 39.3% and 59.8% of men were on any kind of blood pressure (BP)-lowering medication, lipid-lowering medication, or antiplatelet therapy for primary and secondary prevention, respectively. Women with established CVD were significantly less likely than men to receive BP-lowering medications (OR, 0.79 [95% CI, 0.65-0.95]), lipid-lowering medications (OR, 0.69 [95% CI, 0.56-0.84]), antiplatelets (OR, 0.53 [95% CI, 0.45-0.62]), or any CVD prevention medication (OR, 0.62 [95% CI, 0.52-0.73]). Women with established CVD, however, had better BP control (OR, 1.31 [95% CI, 1.14-1.50]) but less well-controlled low-density lipoprotein cholesterol (OR, 0.66 [95% CI, 0.57-0.76]), and were less likely to smoke (OR, 13.89 [95% CI, 11.24-17.15]) and achieve physical activity targets (OR, 1.92 [95% CI, 1.61-2.29]). Conversely, women with high CVD risk were less likely than men to have their BP, low-density lipoprotein cholesterol, and bodyweight controlled (OR, 0.46 [95% CI, 0.38-0.55]; OR, 0.60 [95% CI, 0.52-0.69]; OR, 0.55 [95% CI, 0.48-0.63], respectively), despite a higher use of BP-lowering medications (OR, 1.21 [95% CI, 1.01-1.45]). Younger patients (<65 years) with established CVD were less likely to be taking CVD preventive medications, but there were no sex differences by area of residence or education level. CONCLUSIONS: Large and variable gaps in primary and secondary CVD prevention exist in China, particularly for women. Effective CVD prevention requires an improved overall nationwide strategy and a special emphasis on women with established CVD, who have the greatest disparity and the most to benefit.

The molecular mechanisms underlying anthracyclines-induced cardiotoxicity have not been well elucidated. MiRNAs were revealed dysregulated in the myocardium and plasma of rats received Dox treatment. MicroRNA-34a-5p (miR-34a-5p) was verified increased in the myocardium and plasma of Dox-treated rats, but was reversed in rats received Dox plus DEX treatments. Human miR-34a-5p was also observed increased in the plasma of patients with diffuse large B-cell lymphoma after 9- and 16-week epirubicin therapy. Up-regulation of miR-34a-5p was observed in Dox-induced rat cardiomyocyte H9c2 cells. MiR-34a-5p could augment Bax expression, but inhibited Bcl-2 expression, along with the increases of the activated caspase-3 and mitochondrial potentials in H9C2 cells. MiR-34a-5p was verified to modulate Sirt1 expression post-transcriptionally. In parallel to Sirt1 siRNA, miR-34a-5p could enhance p66shc expression, accompanied by increases of Bax and the activated caspase-3 and a decrease of Bcl-2 in H9c2 cells. Moreover, enforced expression of Sirt1 alleviated Dox-induced apoptosis of H9c2 cells, with suppressing levels of p66shc, Bax, the activated caspase-3 and miR-34a-5p, and enhancing Bcl-2 expression. Therefore, miR-34a-5p enhances cardiomyocyte apoptosis by targeting Sirt1, activation of miR-34a-5p/Sirt1/p66shc pathway contributes to Dox-induced cardiotoxicity, and blockage of this pathway represents a potential cardioprotective effect against anthracyclines.

The angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis (ACE2-Ang-[1-7]-MAS axis) plays an important role in the control of blood pressure. Some previous studies indicated that the genetic variants of ACE2 may have a potential to influence this axis. Therefore, the present study aimed at examining the association of ACE2 polymorphisms with circulating ACE2 and Ang-(1-7) levels in patients with essential hypertension.Hypertensive patients who met the inclusion criteria were enrolled in the present study. Three Tag single-nucleotide polymorphisms (rs2106809, rs4646155, and rs879922) in ACE2 gene were genotyped for all participants. Circulating ACE2 and Ang-(1-7) levels were detected by enzyme-linked immunosorbent assay.There were 96 (53.0%) females and 85 (47.0%) males participating in the present study. The circulating Ang-(1-7) levels were significantly greater in female patients carrying the rs2106809 CC or CT genotype compared with those carrying the TT genotype (1321.9 ± 837.4 or 1077.5 ± 804.4 pg/mL vs 751.9 ± 612.4 pg/mL, respectively; P = 0.029, analysis of variance), whereas the circulating Ang-(1-7) levels were comparable among genotypes in male patients. In addition, there was no significant difference in the circulating ACE2 levels among rs2106809 CC, CT, and TT genotype groups in both female and male patients. The circulating ACE2 and Ang-(1-7) levels were related to neither rs4646155 nor rs879922 in female or male patients.In conclusion, the rs2106809 polymorphism of the ACE2 gene may be a determinant of the circulating Ang-(1-7) level in female patients with hypertension, suggesting a genetic association between circulating Ang-(1-7) levels and ACE2 gene polymorphisms in patients with hypertension.