Myocardial infarction (MI) is an acute coronary syndrome that refers to tissue infarction of the myocardium. This study aimed to investigate the effect of long intergenic non-protein-coding RNA (lincRNA) ATPase plasma membrane Ca 2+ transporting 1 antisense RNA 1 (ATP2B1-AS1) against MI by targeting nuclear factor-kappa-B inhibitor alpha (NFKBIA) and mediating the nuclear factor-kappa-B (NF-κB) signalling pathway. An MI mouse model was established and identified by cardiac function evaluation. It was determined that ATP2B1-AS1 was highly expressed, while NFKBIA was poorly expressed and NF-κB signalling pathway was activated in MI mice. Cardiomyocytes were extracted from mice and introduced with a series of mouse ATP2B1-AS1 vector, NFKBIA vector, siRNA-mouse ATP2B1-AS1 and siRNA-NFKBIA. The expression of NF-κBp50, NF-κBp65 and IKKβ was determined to identify whether ATP2B1-AS1 and NFKBIA affect the NF-κB signalling pathway, the results of which suggested that ATP2B1-AS1 down-regulated the expression of NFKBIA and activated the NF-κB signalling pathway in MI mice. Based on the data from assessment of cell viability, cell cycle, apoptosis and levels of inflammatory cytokines, either silencing of mouse ATP2B1-AS1 or overexpression of NFKBIA was suggested to result in reduced cardiomyocyte apoptosis and expression of inflammatory cytokines, as well as enhanced cardiomyocyte viability. Our study provided evidence that mouse ATP2B1-AS1 silencing may have the potency to protect against MI in mice through inhibiting cardiomyocyte apoptosis and inflammation, highlighting a great promise as a novel therapeutic target for MI. K E Y W O R D Smouse ATPase plasma membrane Ca 2+ transporting 1 antisense RNA 1, myocardial infarction, NF-kappa-B inhibitor alpha, nuclear factor-kappa-B signalling pathway | INTRODUC TI ONMyocardial infarction (MI) is a major public health concern that is commonly known as a heart attack characterized by a decline or complete stop of blood flow to the heart. 1 Since 1998, age-standardized AMI incidence decreased from 323 to 210 per 100 000 in 2007 in female and from 620 to 380 per 100 000 in 2007 in male, but socio-economic inequalities still exist in AMI incidence and have not narrowed. 2 In America, more than one million patients are | 4467 SONG et al.hospitalized due to MI annually, and the rates of readmission are approximately 20% within 30 days after discharge. 3 Moreover, the incidence of MI is increasing in China, and 23 million patients are estimated to experience MI by the end of 2030. 4 The risk factors of MI include hypertension, hypercholesterolaemia, diabetes, smoking habit, obesity, a sedentary lifestyle, excessive alcohol intake and unhealthy diet. 5,6 Earlier recognition or diagnosis of MI symptoms and prompt care-seeking actions are of great significance for the selection of the most appropriate treatments. 7 Although great improvements have been achieved in the prevention and therapies of MI, the difficulties in the prevention of MI are still steadily increasing. 8 Thus, further ef...
Vascular calcification is highly prevalent in patients with type 2 diabetes mellitus (T2DM), one of the most common chronic diseases with high morbidity and mortality.In recent years, microRNAs have been widely reported as potential biomarkers for the diagnosis and treatment of T2DM. We hypothesized that miR-128-3p is associated with cardiovascular calcification and insulin resistance (IR) in rats with T2DM by targeting ISL1 via the Wnt pathway. Microarray analysis was adopted to identify differentially expressed genes related to T2DM. T2DM models were induced in rats. Blood samples from normal and T2DM rats were used to detect islet β-cell function, islet sensitivity, and calcium content. Next, islet tissues were obtained to identify the expression of miR-128-3p, ISL1, and the Wnt signaling pathway-and apoptosis-related genes. Finally, apoptosis of islet β-cells was determined by flow cytometry. Through microarray analysis of GSE27382 and GSE23343, ISL1 was found to be downregulated in T2DM. In blood samples from T2DM rats, basic biochemical indicators, IR, and calcium content were increased, and islet sensitivity and islet β-cell function were decreased. Furthermore, upregulation of miR-128-3p and ISL1 gene silencing promoted the expression of Wnt-1, β-catenin, GSK-3β, and Bax and the phosphorylation of β-catenin and GSK-3β, inhibited c-fos, PDX-1, and Bcl-2 expression, and enhanced cell apoptosis. The key findings of our study demonstrate that miR-128-3p aggravates cardiovascular calcification and IR in T2DM rats by downregulating ISL1 through the activation of the Wnt pathway. Thus, miR-128-3p may serve as a potential target for the treatment of T2DM.
Cardiovascular diseases are a major cause of mortality and disability worldwide. The present study investigated the cardio-protective effects of polysaccharides extracted from Lycium barbarum (LB), the fruit of which is traditionally used in Chinese medicine. Polysaccharides were characterized using Fourier transform infrared spectroscopy and high‑performance liquid chromatography techniques. The present study demonstrated that LB polysaccharides are composed of glucose and fructose monosaccharides in a molar ratio of 1:2. A total of 36 rats were divided into three groups plus a control group, with nine animals in each group, and were used for studying the cardioprotective effects of LB polysaccharides. The low‑dose group received 150 mg/kg body weight (BW) polysaccharides and the high‑dose group received 300 mg/kg BW polysaccharides. The results demonstrated that the LB polysaccharides reduced the levels of myocardial lactate dehydrogenase and increased the sodium‑potassium ATPase and calcium ATPase activities in rats with heart ischemia‑reperfusion injury. In addition, there was a decrease in the myocardial Bax‑positive expression and the rate of myocardial cell apoptosis, along with a dose‑dependent increase in Bcl‑2‑positive expression. Therefore, it was concluded that LB polysaccharides are able to halt the progression of cardiovascular diseases.
BackgroundCardiovascular diseases (CVDs) are the leading causes of mortality worldwide. Currently, the best treatment options for myocardial infarction focus on the restoration of blood flow as soon as possible, which include reperfusion therapy, percutaneous coronary intervention, and therapeutic thrombolytic drugs.Materials and methodsIn the present study, we report the development of lipid-polymeric nanocarriers (LPNs) for mitochondria-targeted delivery of tanshinone IIA (TN). D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was linked to the triphenylphosphonium (TPP) cation. The LPNs were fabricated by nanoprecipitation method. LPNs were evaluated in vitro and in vivo in comparison with free drugs and other similar nanocarriers.ResultsThe mean diameter of TN/nanoparticles (NPs) was 89.6 nm, while that of TN/LPNs was 121.3 nm. The zeta potential of TN/NPs and TN/LPNs was −33.6 and −22.3 mV, respectively. Compared with free TN and TN/NPs, TN/LPNs exhibited significantly improved compatibility and therapeutic efficiency. In addition, the in vivo pharmacokinetics, biodistribution, and infarct therapy studies in Sprague Dawley rats showed that TPP-TPGS/TN/LPNs had better efficiency than their nonmodified TN/LPNs counterparts in all respects.ConclusionThese results indicated that the TPP-TPGS/TN/LPNs were promising nanocarriers for efficient delivery of cardiovascular drugs and other therapeutic agents for the treatment of CVDs.
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