CBL knockdown protects cardiomyocytes against hypoxia-reoxygenation injury by downregulating GRB2 expression.

Myocardial ischemia-reperfusion injury (MIRI) is an event that follows a myocardial infarction. As such, close observation and appropriate patient management is paramount in the treatment process of interventional surgery. The pathogenesis of MIRI has not been fully elucidated. Therefore, the aim of the present study was to explore of novel targets for MIRI treatment whilst also determining their possible underlying mechanism of action. The plasma samples used in the present study were collected from 30 patients with ischemic cardiomyopathy and 30 healthy volunteers. H9c2 rat cardiomyoblasts were subjected to hypoxia and reoxygenation (H/R) modeling to establish an in vitro MIRI model. Initially, the expression levels of Cbl proto-oncogene (CBL) in ICM heart tissue, normal heart tissue, H/R-induced H9c2 cells and normal H9c2 cells were detected using quantitative PCR and western blotting. With the application of Cell Counting Kit-8, western blotting and Tunnel assay, the proliferation, oxidative stress and apoptosis of H/R-induced cells were assessed. Moreover, co-IP assay was employed to testify the interaction between CBL and GRB2. The present study revealed that CBL expression was upregulated in patients with ischemic cardiomyopathy and H/R-induced H9c2 cells in comparison with that in normal heart tissue and normal H9c2 cells, respectively. The genetic silence of CBL using small interfering RNA promoted the proliferation and oxidative stress of H/R-induced cells but repressed the apoptosis. The full-length wild-type of growth factor receptor-bound protein 2 (GRB2) was ligated into pcDNA3.1 to achieve GRB2 overexpression, which revealed that GRB2 overexpression reversed the effects of CBL knockdown on cells, suggesting that it may mediate these processes downstream. In conclusion, under hypoxic conditions, CBL knockdown promoted the proliferation and antioxidant capacity of cardiomyocytes whilst inhibiting apoptosis, by downregulating GRB2 expression. These findings revealed the underlying mechanism of action of this pathway, which can be exploited for the prevention or treatment of MIRI.

Plasma intermedin levels in patients with acute myocardial infarction.

It has been shown that adrenomedullin (ADM) may function as a cardiovascular-regulatory peptide in humans. Intermedin (IMD) is a newly discovered peptide related to ADM and has a greater range of biological effects on the cardiovascular in animal experiments. The purpose of the study was to investigate the pathophysiological role of IMD in patients with acute myocardial infarction (AMI). The present study included twenty patients with acute ST-segment elevation myocardial infarction (STEMI), thirty-three with stable coronary heart disease (SCHD), and eighteen healthy controls. Plasma levels of IMD, malonaldehyde (MDA), and superoxide dismutase (SOD) and cardiac biomarkers were determined at one, two, four and seven days following AMI. Plasma IMD levels were significantly increased on day 1 in AMI patients when compared with SCHD subjects (P=0.014), and reached a peak of 181.88 ± 9.47 pg/ml at 96 h. Plasma IMD concentrations were correlated with MDA and SOD. Furthermore, patients with severe lesions in their coronary arteries tended to have higher plasma IMD levels (P<0.05) in AMI patients. A significant increase in plasma IMD following AMI may be associated with oxidative stress, and could be used as a marker to reflect the severity of the coronary stenosis.

Over time, do anthropometric measures still predict diabetes incidence in chinese han nationality population from chengdu community?

Objective. To examine whether anthropometric measures could predict diabetes incidence in a Chinese population during a 15-year follow-up. Design and Methods. The data were collected in 1992 and then again in 2007 from the same group of 687 individuals. Waist circumference, body mass index, waist to hip ratio, and waist to height ratio were collected based on a standard protocol. To assess the effects of baseline anthropometric measures on the new onset of diabetes, Cox's proportional hazards regression models were used to estimate the hazard ratios of them, and the discriminatory power of anthropometric measures for diabetes was assessed by the area under the receiver operating curve (AROC). Results. Seventy-four individuals were diagnosed with diabetes during a 15-year follow-up period (incidence: 10.8%). These anthropometric measures also predicted future diabetes during a long follow-up (P < 0.001). At 7-8 years, the AROC of central obesity measures (WC, WHpR, WHtR) were higher than that of general obesity measures (BMI) (P < 0.05). But, there were no significant differences among the four anthropometric measurements at 15 years. Conclusions. These anthropometric measures could still predict diabetes with a long time follow-up. However, the validity of anthropometric measures to predict incident diabetes may change with time.