Sarcoplasmic reticulum Ca-ATPase-phospholamban interactions and dilated cardiomyopathy.
Dilated cardiomyopathy is a disease of the heart muscle resulting from a diverse array of conditions that damages the heart and impairs myocardial function. Heart failure occurs when the heart is unable to pump blood at a rate which can accommodate the heart muscle's metabolic requirements. Several signaling pathways have been shown to be involved in the induction of cardiac disease and heart failure. Many of these pathways are linked to cardiac sarcoplasmic reticulum (SR) Ca cycling directly or indirectly. A large body of evidence points to the central role of abnormal Ca handling by SR proteins, Ca-ATPase pump (SERCA2a) and phospholamban (PLN), in pathophysiological heart conditions, compromising the contractile state of the cardiomyocytes. This review summarizes studies which highlight the key role of these two SR proteins in the regulation of cardiac function, the significance of SERCA2a-PLN interactions using transgenic approaches, and the recent discoveries of human PLN mutations leading to disease states. Finally, we will discuss extrapolation of experimental paradigms generated in animal models to the human condition.
Haghighi
Kobra
K
Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
Gregory
Kimberly N
KN
Kranias
Evangelia G
EG
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002311:Cardiomyopathy, Dilated / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009200:Myocardial Contraction; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban