A molecular link between metabolic syndrome and energy metabolism in the heart

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We have identified a novel gene, termed ARIA. ARIA is abundantly expressed in endothelial cells to regulate endothelial angiogenic functions. ARIA interacts with PTEN, a phosphatase that antagonizes PI3K signaling. Since ARIA is a membrane protein, interaction with ARIA leads to the increased membrane-association of PTEN. This increased membrane-association of PTEN causes enhanced inhibition of PI3K signaling that potently regulates cellular apoptosis. Here we found that ARIA is expressed in cardiomyocyte as well, and it regulates cardiac functions. ARIA regulates PI3K/Akt signaling in the heart, and loss of ARIA enhanced cardiac PI3K/Akt signals, leading to the resistance to cardiomyocyte apoptosis and to the stress-induced cardiomyopathy. As PI3K/Akt is a major signaling pathway for insulin, and ARIA potentially modulates the progression of obesity through a modification of adipose tissue angiogenesis, ARIA might provide a novel link between metabolic syndrome and cardiac functions.