The Role of the Protein Phosphatase 1 Inhibitor-1 in Regulation of Murine Cardiac Physiology and Progression of Cardiomyopathy
Year: 2006
Type: article
Abstract: The role of the protein phosphatase 1 inhibitor-1 in the regulation of cardiac physiology and the progression of cardiomyopathy was investigated in this study.Overexpression of the active inhibitor-1 in the murine heart resulted in hyperdynamic myocardial function, linked to specific modulation in the phosphorylation levels of phospholamban, an inhibitor of the sarcoplasmic reticulum ATPase (SERCA).Inhibitor-1 expressing cardiomyocytes exhibited enhanced calcium cycling linked to reduced inhibition of SERCA by the phosphorylated phospholamban.The inhibitor-1 overexpressing mouse was also challenged with the stress of chronic pressure overload.Interestingly, inhibitor-1 expression, in this stress model, completely protected against functional decline and was associated with reduced hypertrophy.At the molecular level, increased phosphorylation of phospholamban (serine-16) persisted in banded inhibitor-1 mice.The effects of inhibitor-1 expression were also studied as a molecular intervention in a rat model of heart failure, generated by chronic pressure overload.Therapeutic gene transfer of inhibitor-1 in failing rat hearts, resulted in restoration of cardiac function towards normal, and was also associated with increased phosphorylation of phospholamban at serine-16.All in all, these studies provide significant support for the potential of inhibitor-1, as a therapeutic target; however, more extensive studies in larger animal models and more controlled expression systems are required for further validation of inhibitor-1 as a molecular target in heart failure.
Author: Anand Pathak
Institution: University of Cincinnati
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2207301306