Palmitic acid (PA) can induce lipotoxic damage to cardiomyocytes, although its precise mechanism of action has not been completely elucidated. Growth arrest-specific transcript 5 (GAS5) is a long noncoding RNA that serves a regulatory role in several pathological processes, including tumorigenesis, stroke, cardiac fibrosis and osteoarthritis; however, its role in PA-induced myocardial injury remains elusive. The present study aimed to explore the role and underlying mechanism of GAS5 on PA-induced myocardial injury. The expression of GAS5 in PA-treated cardiomyocytes (H9c2 cells) was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and its effects on PA-induced myocardial injury were measured by Cell Counting Kit-8 and lactate dehydrogenase (LDH) assays. The activities of cytokines and nuclear factor (NF)-κB were also detected by enzyme-linked immunosorbent assay, while interactions between GAS5 and microRNA (miR)-26a were evaluated by luciferase reporter assay and RT-qPCR. The regulation of GAS5 on high mobility group box 1 (HMGB1) expression was detected by RT-qPCR and western blotting. The results demonstrated that GAS5 was significantly upregulated in cardiomyocytes following treatment with PA. GAS5-knockdown increased the viability of PA-treated cardiomyocytes and reduced the activity of LDH, tumor necrosis factor-α and interleukin-1β. Furthermore, the present study identified that GAS5 specifically binds to miR-26a, and a reciprocal negative regulation exists between the two. The present study also demonstrated that GAS5 downregulation inhibited HMGB1 expression and NF-κB activation, while these suppressive effects were mediated by miR-26a. In conclusion, the present study demonstrated that PA can induce GAS5 expression and that the downregulation of GAS5 alleviated PA-induced myocardial inflammatory injury through the miR-26a/HMGB1/NF-κB axis. These data may provide a novel insight into the mechanism of myocardial lipotoxic injury.

Aims: Sweroside, a secoiridoid glucoside extracted from Swertia pseudochinensis Hara, is reported to possess antioxidant and anti-inflammatory activities. However, whether sweroside has a protective effect on myocardial ischemia–reperfusion (IR) injury is yet to be elucidated. The present study aimed to confirm the cardioprotective effect of sweroside and to identify its underlying mechanism.Methods and Results: H9c2 cells were pretreated with sweroside and then underwent hypoxia–reoxygenation. Cell Counting Kit-8, creatine kinase-myocardial band (CK-MB) and lactate dehydrogenase (LDH) assays were conducted to detect cell viability and myocardial injury, respectively. The Langendorff method was used to induce myocardial IR injury ex vivo. Triphenyltetrazolium chloride staining was performed to detect myocardial infarct size, while protein expression was analyzed using western blotting. Overall, the results indicated that sweroside pretreatment dose-dependently led to a significant enhancement in cell viability, a decrease in release of CK-MB and LDH, a reduction in infarct size, and an improvement in cardiac function. Additionally, sweroside pretreatment caused a marked suppression of oxidative stress, as evidenced by the fact that sweroside decreased the accumulation of reactive oxygen species and malondialdehyde, while enhancing the activities of superoxide dismutase and glutathione peroxidase. Moreover, sweroside was found to notably repress pyroptosis, as sweroside blocked pore formation in the cell membrane, inhibited caspase-1 and interleukin (IL)-1β activity, and decreased the expression levels of NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD, cleaved caspase-1, and IL-1β. Mechanistically, it was found that sweroside inhibited Kelch-like ECH-associated protein 1 (Keap1) and induced nuclear factor E2-associated factor 2 (Nrf2) nuclear translocation. Furthermore, the inhibition of oxidative stress and pyroptosis by sweroside could be abrogated via the inhibition of Nrf2 expression, which suggested that the protective effect induced by sweroside was Nrf2-dependent.Conclusions: The present study demonstrated that sweroside pretreatment could protect against myocardial IR injury by inhibiting of oxidative stress and NLRP3 inflammasome-mediated pyroptosis partially via modulation of the Keap1/Nrf2 axis.

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The purpose of this study was to investigate the underlying mechanism of cardiac contractility modulation (CCM) in improving trans aortic constriction (TAC)-induced heart failure (HF) left ventricular (LV) systolic function. A total of 25 New Zealand white rabbits were randomly divided into 5 groups: sham operation group (SHM), TAC-induced HF group (HF), TAC-induced HF followed by CCM stimulation group (HF + CCM), TAC-induced HF followed by injection of anti-miR-25 group (HF + anti-miR-25), TAC-induced HF followed by CCM stimulation and AAV9-miR-25 injection group (HF + CCM + miR-25). CCM current was performed 6 hours a day for 4 weeks. The left ventricle ejection fraction (LVEF) was measured by ultrasound. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used for measuring RNA and protein levels. The sarcoplasmic reticulum calcium ATPase (SERCA2A) and LVEF were reduced, while the miR-25 expression was improved in HF group compared to SHM group. Conversely, the SERCA2A and LVEF were improved, and the miR-25 reduced in the HF + CCM and the HF + anti-miR-25 groups compared to the HF group. Moreover, the SERCA2A and LVEF were reduced, while the miR-25 was improved in the HF + CCM + miR-25 group compared to the HF + CCM group. CCM is a potentially effective procedure for improving LV systolic function, which might partially by inhibiting miR-25 expression, further improved SERCA2A expression in TAC HF models.

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This article has been peer reviewed and published immediately upon acceptance. It is an open access article, which means that it can be downloaded, printed, and distributed freely, provided the work is properly cited. Articles in "Cardiology Journal" are listed in PubMed.

Background: Coronary slow flow phenomenon (CSFP) involves the delayed opacification of the coronary distal vessel, in the absence of an obstructive lesion in the epicardial coronary artery during angiography. Since the link between left atrial (LA) function and decreased left ventricular function is still unclear, we evaluated LA function using real-time three-dimensional echocardiography (RT3DE) in patients with CSFP, and subsequently determined the incremental value of RT3DE. Methods: This study enrolled 60 patients with CSFP and 45 control subjects. CSFP was diagnosed based on thrombolysis in myocardial infarction frame count (TFC). The LA phasic volume and function was evaluated by both two-dimensional echocardiography (2DE) and RT3DE.