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Publication
Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity.
RATIONALE: Previously, we demonstrated that a deoxycorticosterone acetate (DOCA)-salt hypertensive mouse model produces cardiac oxidative stress and diastolic dysfunction with preserved systolic function. Oxidative stress has been shown to increase late …
Publication
Sildenafil reverses cardiac dysfunction in the mdx mouse model of Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a progressive and fatal genetic disorder of muscle degeneration. Patients with DMD lack expression of the protein dystrophin as a result of mutations in the X-linked dystrophin gene. The loss of dystrophin leads to …
Publication
Mitigation of the progression of heart failure with sildenafil involves inhibition of RhoA/Rho-kinase pathway.
Chronic inhibition of phosphodiesterase-5 with sildenafil immediately after permanent occlusion of the left anterior descending coronary artery was shown to limit ischemic heart failure (HF) in mice. To mimic a more clinical scenario, we postulated that …
Publication
Farnesyltransferase Inhibitor FTI-277 Reduces Mortality of Septic Mice along with Improved Bacterial Clearance
Treatment with statins, inhibitors of HMG-CoA reductase, ex- tends the survival of septic mice. However, the molecular mechanisms underlying the cholesterol-lowering, independent beneficial effects of statins in sepsis are poorly understood. The …
Publication
Quantitative characterization of postnatal growth trends in proximal pulmonary arteries in rats by phase-contrast magnetic resonance imaging.
Malformations of the pulmonary arteries can increase right heart workload and result in morbidity, heart failure, and death. With the increased use of murine models to study these malformations, there is a pressing need for an accurate and noninvasive …
Publication
Dimethylarginine dimethylaminohydrolase-1 is the critical enzyme for degrading the cardiovascular risk factor asymmetrical dimethylarginine.
OBJECTIVE: The objective of this study was to identify the role of dimethylarginine dimethylaminohydrolase-1 (DDAH1) in degrading the endogenous nitric oxide synthase inhibitors asymmetrical dimethylarginine (ADMA) and N(g)-monomethyl-L-arginine (L-NMMA). …
Publication
Phosphoinositide 3-kinase γ inhibits cardiac GSK-3 independently of Akt.
Activation of cardiac phosphoinositide 3-kinase α (PI3Kα) by growth factors, such as insulin, or activation of PI3Kγ downstream of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors stimulates the activity of the kinase Akt, …
Publication
Oxidative Stress Regulates Left Ventricular PDE5 Expression in the Failing Heart
BACKGROUND: Phosphodiesterase type 5 (PDE5) inhibition has been shown to exert profound beneficial effects in the failing heart, suggesting a significant role for PDE5 in the development of congestive heart failure (CHF). The purpose of this study is to …
Publication
High intake of saturated fat, but not polyunsaturated fat, improves survival in heart failure despite persistent mitochondrial defects.
AIMS: The impact of a high-fat diet on the failing heart is unclear, and the differences between polyunsaturated fatty acids (PUFA) and saturated fat have not been assessed. Here, we compared a standard low-fat diet to high-fat diets enriched with either …
Publication
Obesity suppresses circulating level and function of endothelial progenitor cells and heart function
BACKGROUND AND AIM: This study tested the hypothesis that obesity suppresses circulating number as well as the function of endothelial progenitor cells (EPCs) and left ventricular ejection fraction (LVEF). METHODS: High fat diet (45 Kcal% fat) was given …