Sodium potassium adenosine triphosphatase (Na/K-ATPase) as a therapeutic target for uremic cardiomyopathy.
Clinically, patients with significant reductions in renal function present with cardiovascular dysfunction typically termed, uremic cardiomyopathy. It is a progressive series of cardiac pathophysiological changes, including left ventricular diastolic dysfunction and hypertrophy (LVH) which sometimes progress to left ventricular dilation (LVD) and systolic dysfunction in the setting of chronic kidney disease (CKD). Uremic cardiomyopathy is almost ubiquitous in patients afflicted with end stage renal disease (ESRD). Areas covered: This article reviews recent epidemiology, pathophysiology of uremic cardiomyopathy and provide a board overview of Na/K-ATPase research with detailed discussion on the mechanisms of Na/K-ATPase/Src/ROS amplification loop. We also present clinical and preclinical evidences as well as molecular mechanism of this amplification loop in the development of uremic cardiomyopathy. A potential therapeutic peptide that targets on this loop is discussed. Expert opinion: Current clinical treatment for uremic cardiomyopathy remains disappointing. Targeting the ROS amplification loop mediated by the Na/K-ATPase signaling function may provide a novel therapeutic target for uremic cardiomyopathy and related diseases. Additional studies of Na/K-ATPase and other strategies that regulate this loop will lead to new therapeutics.
a Joan C Edwards School of Medicine at Marshall University , Huntington , WV , United States.|b University of Toledo College of Medicine and Life Sciences , Toledo , OH , United States.
Xiaoliang
X
Wang
a Joan C Edwards School of Medicine at Marshall University , Huntington , WV , United States.
Jiang
J
Liu
b University of Toledo College of Medicine and Life Sciences , Toledo , OH , United States.
Christopher A
CA
Drummond
a Joan C Edwards School of Medicine at Marshall University , Huntington , WV , United States.
Joseph I
JI
Shapiro
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications; D058990:Molecular Targeted Therapy; D010455:Peptides / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014511:Uremia / Q000150:complications*; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology
D010455:Peptides; D017382:Reactive Oxygen Species; D000254:Sodium-Potassium-Exchanging ATPase
Na/K-ATPase; ROS; cell signaling; uremic cardiomyopathy