LncRNA-GAS5 regulates PDCD4 expression and mediates myocardial infarction-induced cardiomyocytes apoptosis via targeting MiR-21.

The present study was designed to investigate whether and how lncRNA-GAS5 regulates cardiomyocyte apoptosis in MI. MI rat model was established by the left anterior descending (LAD) coronary artery ligation. MI model was further evaluated by biomarkers detection and TUNEL, HE and Masson staining. The roles of lncRNA-GAS5 on hypoxia/reoxygenation (H/R)-induced cardiomyocytes survival, cell cycle arrest, and apoptosis were examined by MTT and flow cytometry in rat heart-derived H9c2 cells. Western blot was used to determine the effect of GAS5 on the expression of apoptosis-associated proteins and PI3 K/AKT signaling pathway. The direct bindings of GAS5 to miR-21 and miR-21 to PDCD4 were measured by dual-luciferase reporter assay or RNA immunoprecipitation. Decreased expressions of GAS5 and PDCD4 as well as increased miR-21 level were observed in the hearts of MI-modeled rat, accompanying with morphologically myocardial cell injury, as well as collagen deposition and fibrosis, and elevated levels of cTnl, CK, CK-MB and LDH. In the cell model, the knockdown of GAS5 promoted cell survival, prevented cell cycle arrest and inhibited cell apoptosis while the overexpression of GAS5 showed the opposite effects. GAS5 was found to downregulate miR-21 and the effects of GAS5 were attenuated by miR-21 mimics. GAS5 positively regulated PDCD4 expression by functioning as a sponge of miR-21 in H/R model. Moreover, GAS5 stimulated PDCD4 and suppressed PI3 K/AKT signal pathway. LncRNA-GAS5 regulates PDCD4 expression to mediate MI-induced cardiomyocyte apoptosis via targeting miR-21, suggesting that GAS5 could be a therapeutic target for MI.

Association between obesity and ECG variables in children and adolescents: A cross-sectional study.

Obesity exhibits a wide variety of electrocardiogram (ECG) abnormalities in adults, which often lead to cardiovascular events. However, there is currently no evidence of an association between obesity and ECG variables in children and adolescents. The present study aimed to explore the associations between obesity and ECG intervals and axes in children and adolescents. A cross-sectional observational study of 5,556 students aged 5-18 years was performed. Anthropometric data, blood pressure and standard 12-lead ECGs were collected for each participant. ECG variables were measured manually based on the temporal alignment of simultaneous 12 leads using a CV200 ECG Work Station. Overweight and obese groups demonstrated significantly longer PR intervals, wider QRS durations and leftward shifts of frontal P-wave, QRS and T-wave axes, while the obese group also demonstrated significantly higher heart rates, compared with normal weight groups within normotensive or hypertensive subjects (P<0.05). Abdominal obesity was also associated with longer PR intervals, wider QRS duration and a leftward shift of frontal ECG axes compared with normal waist circumference (WC) within normotensive or hypertensive subjects (P<0.05). Gender was a possible factor affecting the ECG variables. Furthermore, the ECG variables, including PR interval, QRS duration and frontal P-wave, QRS and T-wave axes, were significantly linearly correlated with body mass index, WC and waist-to-height ratio adjusted for age, gender, ethnicity and blood pressure. However, there was no significant association between obesity and the corrected QT interval (P>0.05). The results of the current study indicate that in children and adolescents, general and abdominal obesity is associated with longer PR intervals, wider QRS duration and a leftward shift of frontal P-wave, QRS and T-wave axes, independent of age, gender, ethnicity and blood pressure.