Tumor suppressor Ras-association domain family 1 isoform A is a novel regulator of cardiac hypertrophy

BACKGROUND: Ras signaling regulates a number of important processes in the heart, including cell growth and hypertrophy. Although it is known that defective Ras signaling is associated with Noonan, Costello, and other syndromes that are characterized by tumor formation and cardiac hypertrophy, little is known about factors that may control it. Here we investigate the role of Ras effector Ras-association domain family 1 isoform A (RASSF1A) in regulating myocardial hypertrophy.

METHODS AND RESULTS: A significant downregulation of RASSF1A expression was observed in hypertrophic mouse hearts, as well as in failing human hearts. To further investigate the role of RASSF1A in cardiac (patho)physiology, we used RASSF1A knock-out (RASSF1A(-)(/)(-)) mice and neonatal rat cardiomyocytes with adenoviral overexpression of RASSF1A. Ablation of RASSF1A in mice significantly enhanced the hypertrophic response to transverse aortic constriction (64.2% increase in heart weight/body weight ratio in RASSF1A(-)(/)(-) mice compared with 32.4% in wild type). Consistent with the in vivo data, overexpression of RASSF1A in cardiomyocytes markedly reduced the cellular hypertrophic response to phenylephrine stimulation. Analysis of molecular signaling events in isolated cardiomyocytes indicated that RASSF1A inhibited extracellular regulated kinase 1/2 activation, likely by blocking the binding of Raf1 to active Ras.

CONCLUSIONS: Our data establish RASSF1A as a novel inhibitor of cardiac hypertrophy by modulating the extracellular regulated kinase 1/2 pathway.

The impact of parental migration on health status and health behaviours among left behind adolescent school children in China.

BACKGROUND:

One out of ten of China's population are migrants, moving from rural to urban areas. Many leave their families behind resulting in millions of school children living in their rural home towns without one or both their parents. Little is known about the health status of these left behind children (LBC). This study compares the health status and health-related behaviours of left behind adolescent school children and their counterparts in a rural area in Southern China.

METHODS:

A cross-sectional study was conducted among middle school students in Fuyang Township, Guangdong, China (2007-2008). Information about health behaviours, parental migration and demographic characteristics was collected using a self-administered questionnaire. Overweight/obesity and stunting were defined based on measurements of height and weight. Univariate and multivariate analyses were used to estimate the differences in health outcomes between LBC and non-LBC.

RESULTS:

18.1% of the schoolchildren had one or both parents working away from home. Multivariate analysis showed that male LBC were at higher risk of skipping breakfast, higher levels of physical inactivity, internet addiction, having ever smoked tobacco, suicide ideation, and being overweight. LBC girls were more likely to drink excessive amounts of sweetened beverage, to watch more TV, to have ever smoked or currently smoke tobacco, to have ever drunk alcohol and to binge drinking. They were also more likely to be unhappy, to think of planning suicide and consider leaving home.

CONCLUSIONS:

Our findings suggest that parental migration is a risk factor for unhealthy behaviours amongst adolescent school children in rural China. Further research is required in addition to the consideration of the implications for policies and programmes to protect LBC.