APJ acts as a dual receptor in cardiac hypertrophy

Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues. Here we report that genetic loss of APJ, a G-protein-coupled receptor, confers resistance to chronic pressure overload by markedly reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin-independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to stretch, indicating that APJ is a mechanosensor. Activation of APJ by stretch increases cardiomyocyte cell size and induces molecular markers of hypertrophy. Whereas apelin stimulates APJ to activate Gαi and elicits a protective response, stretch signals in an APJ-dependent, G-protein-independent fashion to induce hypertrophy. Stretch-mediated hypertrophy is prevented by knockdown of β-arrestins or by pharmacological doses of apelin acting through Gαi. Taken together, our data indicate that APJ is a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin. By sensing the balance between these stimuli, APJ occupies a pivotal point linking sustained overload to cardiomyocyte hypertrophy.     

Living arrangements among older people: an overview of trends in Europe and the USA

This article compares the trends in living arrangements of older people in several European countries and in the United States. Trends and cross-country variability in several factors that could account for these cross-national differences, including marital status, fertility, labour force participation and attitudes, are also examined. In most countries the proportion of older people living alone increased substantially between 1970 and 1990. However the increase in living alone stabilised or even declined between 1990 and 2000 in most of the countries analysed indicating a possible reversal in the trend. Increases in proportions of older women who are married and reductions in the proportions childless may partially explain this. Considerable variability in both trends and levels of older people's living arrangements was seen especially between north-western and southern European countries. These variations mirrored contrasts in attitudes towards residential care and parent-child coresidence between the countries.