Targeted Sarcoplasmic Reticulum Ca2+ ATPase 2a Gene Delivery to Restore Electrical Stability in the Failing Heart

Recently, we reported that sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a), the pump responsible for reuptake of cytosolic calcium during diastole, plays a central role in the molecular mechanism of cardiac alternans. Heart failure (HF) is associated with impaired myocardial calcium handling, defi...

Full description

Saved in:
Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2012-10, Vol.126 (17), p.2095-2104
Main Authors: CUTLER, Michael J, XIAOPING WAN, PLUMMER, Bradley N, HAIYAN LIU, DESCHENES, Isabelle, LAURITA, Kenneth R, HAJJAR, Roger J, ROSENBAUM, David S
Format: Article
Language:English
Subjects:
Animals
Arrhythmias, Cardiac - enzymology
Arrhythmias, Cardiac - therapy
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Cardiovascular system
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Gene Targeting - methods
Gene Transfer Techniques
Guinea Pigs
Heart Failure - enzymology
Heart Failure - genetics
Heart Failure - therapy
Male
Medical sciences
Miscellaneous
Myocytes, Cardiac - enzymology
Pharmacology. Drug treatments
Sarcoplasmic Reticulum - enzymology
Sarcoplasmic Reticulum - genetics
Sarcoplasmic Reticulum Calcium-Transporting ATPases - administration & dosage
Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Recently, we reported that sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a), the pump responsible for reuptake of cytosolic calcium during diastole, plays a central role in the molecular mechanism of cardiac alternans. Heart failure (HF) is associated with impaired myocardial calcium handling, deficient SERCA2a, and increased susceptibility to cardiac alternans. Therefore, we hypothesized that restoring deficient SERCA2a by gene transfer will significantly reduce arrhythmogenic cardiac alternans in the failing heart. Adult guinea pigs were divided into 3 groups: control, HF, and HF+AAV9.SERCA2a gene transfer. HF resulted in a decrease in left ventricular fractional shortening compared with controls (P
ISSN:0009-7322
1524-4539
DOI:10.1161/circulationaha.111.071480