Cardiac hypertrophy is one of the major risk factors of cardiovascular morbidity and mortality. Autophagy is acknowledged to be an important mechanism regulating cardiac hypertrophy. Sestrin 1, a downstream target gene of p53, has been proven to regulate autophagy. However, the role of Sestrin 1 in cardiac hypertrophy remains unknown. Our study showed that Sestrin 1 mRNA and protein expression declined in pressure overload cardiac hypertrophy and phenylephrine (PE)‐induced cardiac hypertrophy. Knockdown of Sestrin 1 by RNAi deteriorated PE‐induced cardiac hypertrophy, whereas the overexpression of Sestrin 1 by adenovirus transfection blunted hypertrophy. We discovered that knockdown of Sestrin 1 resulted in impaired autophagy while overexpression of Sestrin 1 resulted in increased autophagy without affecting lysosomal function. In addition, the antihypertrophic effect of Sestrin 1 overexpression was eliminated by autophagy blockade. Importantly, Sestrin 1 targets at the AMPK/mTORC1/autophagy pathway to inhibit cardiac hypertrophy by interaction with AMPK which is responsible for autophagy regulation. Taken together, our data indicate that Sestrin 1 regulates AMPK/mTORC1/autophagy axis to attenuate cardiac hypertrophy.

Background: Recent studies have reported the effects of metabolic syndrome (MetS) and its components on atrial fibrillation (AF), but the results remain controversial. Therefore, we performed a meta-analysis to evaluate the relationship between MetS and AF risk.Methods: Studies were searched from the Cochrane library, PubMed, and Embase databases through May 2020. Adjusted hazard ratios (HRs) and its corresponding 95% confidence intervals (CIs) were extracted and then pooled by using a random effects model.Results: A total of 6 observational cohort studies were finally included. In the pooled analysis, MetS was associated with an increased risk of AF (HR 1.57; 95% CI 1.40–1.77;P < 0.01). And the components of MetS including abdominal obesity (HR 1.37; 95% CI 1.36–1.38;P < 0.01), elevated blood pressure (HR 1.56; 95% CI 1.46–1.66;P < 0.01), elevated fasting glucose (HR 1.18; 95% CI 1.15–1.21;P < 0.01) and low high density cholesterol (HDL) (HR 1.18; 95% CI 1.06–1.32;P < 0.01) was also associated with an increased risk of AF, while high triglyceride (HR 0.99; 95% CI 0.87–1.11,P = 0.82) was not.Conclusions: Our present meta-analysis suggested that MetS, as well as its components including abdominal obesity, elevated blood pressure, elevated fasting glucose and low HDL cholesterol were associated with an increase in the risk of AF.

Background and Purpose: Several observational studies have compared the effect of the non–vitamin K antagonist oral anticoagulants to each other in patients with atrial fibrillation. However, confounding by indication is a major problem when comparing non–vitamin K antagonist oral anticoagulant treatments in some of these studies. This meta-analysis was conducted to compare the effectiveness and safety between non–vitamin K antagonist oral anticoagulant and non–vitamin K antagonist oral anticoagulant by only including the propensity score matching studies. Methods: We systematically searched the PubMed and Ovid databases until May 2020 to identify relevant observational studies. Hazard ratios (HRs) and 95% CIs of the reported outcomes were collected and then pooled by a random-effects model complemented with an inverse variance heterogeneity or quality effects model. Results: A total of 17 retrospective cohort studies were included in this meta-analysis. Compared with dabigatran use, the use of rivaroxaban was significantly associated with increased risks of stroke or systemic embolism (HR, 1.16 [95% CI, 1.05–1.29]) and major bleeding (HR, 1.32 [95% CI, 1.24–1.41]), whereas the use of apixaban was associated with a reduced risk of major bleeding (HR, 0.78 [95% CI, 0.67–0.90]) but not stroke or systemic embolism (HR, 0.84 [95% CI, 0.56–1.28]). Compared with rivaroxaban use, the use of apixaban was associated with a decreased risk of major bleeding (HR, 0.63 [95% CI, 0.54–0.73]) but not stroke or systemic embolism (HR, 0.83 [95% CI, 0.67–1.04]). Reanalyses with the inverse variance heterogeneity or quality effects model produced similar results as the random-effects model. Conclusions: Current observational comparisons with propensity score matching methods suggest that apixaban might be a better choice compared with dabigatran or rivaroxaban for stroke prevention in atrial fibrillation patients.