Late-life Rapamycin Treatment Enhances Cardiomyocyte Relaxation Kinetics and Reduces Myocardial Stiffness.

Diastolic dysfunction is a key feature of the aging heart. We have shown that late-life treatment with mTOR inhibitor, rapamycin, reverses age-related diastolic dysfunction in mice but the molecular mechanisms of the reversal remain unclear. To dissect the mechanisms by which rapamycin improves diastolic function in old mice, we examined the effects of rapamycin treatment at the levels of single cardiomyocyte, myofibril and multicellular cardiac muscle.

Regulation of cardiac ryanodine receptor function by the cyclic-GMP dependent protein kinase G.

Background: The cGMP-dependent protein kinase G (PKG) phosphorylates the cardiac ryanodine receptor (RyR2) . We aimed to determine whether modulation of endogenous PKG alters RyR2-mediated spontaneous Ca release and whether this effect is linked to a change in RyR2 phosphorylation.

Methods: & Results: Human embryonic kidney (HEK293) cells with inducible RyR2 expression were treated with the cGMP analogue 8-Br-cGMP (100 μM) to activate endogenous PKG.

NAD Redox Imbalance in the Heart Exacerbates Diabetic Cardiomyopathy.

Background: Diabetes is a risk factor for heart failure and promotes cardiac dysfunction. Diabetic tissues are associated with nicotinamide adenine dinucleotide (NAD) redox imbalance; however, the hypothesis that NAD redox imbalance causes diabetic cardiomyopathy has not been tested. This investigation used mouse models with altered NAD redox balance to test this hypothesis.