Sarcoplasmic reticulum Ca²⁺ATPase as a therapeutic target for heart failure

Abstract

Background-The cardiac isoform of the sarco/endoplasmic reticulum Ca 2+ ATPase (SERCA2a) plays a major role in controlling excitation/contraction coupling. In both experimental and clinical heart failure (HF), SERCA2a expression is significantly reduced which leads to abnormal Ca 2+ handling and deficient contractility. A large number of studies in isolated cardiac myocytes, in small and large animal models of HF showed that restoring SERCA2a expression by gene transfer corrects the contractile abnormalities and improves energetics and electrical remodeling. Following a long line of investigation, a clinical trial is underway to restore SERCA2a expression in patients with HF using adeno-associated virus type 1.

Synthetic Phosphopeptides Enable Quantitation of the Content and Function of the Four Phosphorylation States of Phospholamban in Cardiac Muscle

“…Implications for Cardiac Physiology and Pathology-SERCA activation is an established therapeutic goal in treatment of heart failure (65). Therefore, the high concentration of P16-PLB in cardiac tissue homogenates (Fig.…”

Attenuation of Endoplasmic Reticulum Stress-Related Myocardial Apoptosis by SERCA2a Gene Delivery in Ischemic Heart Disease

“…Abnormal calcium handling associated with a decrease in the expression and activity of SERCA2a is suggested to be one of the key abnormalities in a variety of cardiovascular disorders, including heart failure, acute myocardial ischemia and ischemia/perfusion, and chronic myocardial ischemia (3,29,32). A large number of studies in isolated cardiomyocytes and animal models of heart failure showed that restoring SERCA2a expression by gene transfer corrects the contractile dysfunction and energetic and electrical remodeling (29,32).…”

Neurodegeneration in the elderly – When the blood type matters: An overview of the McLeod syndrome with focus on hematological features

“…Gardos channels are ubiquitously expressed in body tissue 79 and their functionality may depend on intact XK protein. In line with this assumption, disruption of XK may therefore lead to multisystem deficiencies by impairment of Gardos functionality which could explain the chef affected cardiac and neuronal tissues in MLS [79][80][81][82][83] (see Table 1). …”