BACKGROUND/AIMS A major challenge for current therapeutic strategies against ischemia/reperfusion (I/R) is the lack of effective drugs. Considering luteolin enhances the activity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) to improve the systolic/diastolic function of rat hearts and cardiomyocytes during the I/R process, we studied the regulatory function of the p38 MAPK pathway in this pro...

Background—Ventricular arrhythmias are life-threatening complications of heart failure and myocardial ischemia. Increased diastolic Ca overload occurring in ischemia leads to afterdepolarizations and aftercontractions that are responsible for cellular electric instability. We inquired whether sarcoplasmic reticulum Ca ATPase pump (SERCA2a) overexpression could reduce ischemic ventricular arrhyt...

Heart disease remains the leading cause of death worldwide, highlighting a pressing need to identify novel regulators of cardiomyocyte (CM) function that could be therapeutically targeted. The mammalian Hippo/Tead pathway is critical in embryonic cardiac development and perinatal CM proliferation. However, the requirement of Tead1, the transcriptional effector of this pathway, in the adult hear...

BACKGROUND Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improving endothelial function in patients with acute myocardial infarction undergoing percutaneous coronary intervention. The present study will investigate whether liraglutide can perfo...

In pulmonary arterial smooth muscle, Ca(2+) release from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) may induce constriction and dilation in a manner that is not mutually exclusive. We show here that the targeting of different sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases (SERCA) and RyR subtypes to discrete SR regions explains this paradox. Western blots identified prote...

BACKGROUND Heart failure often complicates myocardial infarction (MI), and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA2a) is underexpressed in the failing myocardium. We examined the effect of preexisting cardiac SERCA2a protein overexpression on rat survival and left ventricular (LV) remodeling after MI. METHODS AND RESULTS Baseline myocardial SERCA2a expression was 37% higher in t...

Despite intensive interest in the dedifferentiation process of vascular smooth muscle cells, very little data are available on intracellular Ca(2+) signaling. The present study was designed to investigate the evolution of the intracellular Ca(2+) pools when rat aortic smooth muscle cells (RASMCs) proliferate and to define the mechanisms involved in the functional alterations. RASMCs were cultur...

The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) actively transports into the sarcoplasmic to facilitate cardiac muscle relaxation. Phospholamban (PLN) allosterically inhibits SERCA, and an imbalance of SERCA2a, dominant isoform, PLN content disrupts homeostasis contractility. A previous study has shown that ovariectomized (OVX) rats have reduced SERCA activity due lowered SERCA2a increased...

Dilated cardiomyopathy and end-stage heart failure result in multiple defects in cardiac excitation-contraction coupling. Via complementation of a genetically based mouse model of dilated cardiomyopathy, we now provide evidence that progressive chamber dilation and heart failure are dependent on a Ca2+ cycling defect in the cardiac sarcoplasmic reticulum. The ablation of a muscle-specific sarco...