No abstract

Chronic heart failure (CHF) may be associated with an energy deficit in cardiac muscle. As levo-carnitine (LC) is involved in the production of myocardial energy, it is hypothesized that LC supplementation may ameliorate CHF symptoms. This multicentre, randomized, double-blind, and placebo-controlled study included 265 patients with CHF. Patients were randomized to receive either LC or placebo, twice a day. Endpoints were measured after 7 days of treatment. Primary endpoint was a reduction of at least one NYHA class. Secondary endpoints were changes in 6-min walk distance (6-MWD) compared with baseline, either alone or in combination with NYHA class decrease, left ventricular ejection fraction, and NT-proBNP level, together with adverse events. The primary endpoint was reached in 60.9% of patients treated with LC, compared with only 44.7% of the placebo group (P ¼ 0.012). Among the secondary endpoints, 6-MWD, alone or in combination with NYHA class, improved significantly in the LC group compared with placebo (P ¼ 0.0497 and P ¼ 0.003, respectively). values of plasma-free carnitine were observed in patients with NYHA classes III and IV where the effect of LC supplementation was greatest (P ¼ 0.002). Treatment with LC significantly improved CHF symptoms in Chinese patients, probably by correcting a status of carnitine insufficiency.

No abstract

microRNAs (miRs) are essential in the development of heart failure. The aim of this study is to investigate the effect of microRNA‐330 (miR‐330) on left ventricular remodeling via the TGF‐β1/Smad3 signaling pathway by targeting the sex‐determining region Y (SRY) in mice with myocardial ischemia–reperfusion injury (MIRI). Differentially expressed gene (DEG) in myocardial ischemia–reperfusion (IR) was screened out and the miR that targeted the DEG was also predicted and verified. A model of MIRI was established to detect the expression of miR‐330, SRY, transforming growth factor‐β (TGF‐β1), and Sekelsky mothers against dpp3 (Smad3). To further investigate the role of miR‐330 in MIRI with the involvement of SRY and TGF‐β1/Smad3 signaling pathway, the modeled mice were treated with different mimic, inhibitor, or small interfering RNA (siRNA) to observe the changes of the related gene expression, as well as the myocardial infarction size and volume of myocardial collagen. SRY was screened out and verified as a target gene of miR‐330. The MIRI mice showed enlarged myocardial infarction size, increased volume of myocardial collagen, increased expression of miR‐330, TGF‐β1 and Smad3, while decreased the expression of SRY. The MIRI mice treated with miR‐330 inhibitor showed decreased myocardial infarction size, the volume of myocardial collagen, and expression of TGF‐β1 and Smad3 but promoted expression of SRY. Our findings demonstrated that downregulated miR‐330 could suppress left ventricular remodeling to inhibit the activation of the TGF‐β1/Smad3 signaling pathway via negatively targeting of SRY in mice with MIRI. This can be a potential target in the strategy to attenuate patient suffering.