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Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins.

Abstract：

:The aim of this study was to examine whether short- and long-term gene transfer of Ca(2+) handling proteins restore left ventricular (LV) mechanoenergetics in aortic banding-induced failing hearts. Aortic-banded rats received recombinant adenoviruses carrying sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) (Banding+SERCA), parvalbumin (Banding+Parv) or beta-galactosidase (Banding+betagal), or an adeno-associated virus carrying SERCA2a (Banding+AAV.SERCA) by a catheter-based technique. LV mechanoenergetic function was measured in cross-circulated hearts. "Banding", "Banding+betagal" and "Banding+saline" groups showed lower end-systolic pressure at 0.1 ml intraballoon water (ESP(0.1)), higher end-diastolic pressure at 0.1 ml intraballoon water (EDP(0.1)) and slower LV relaxation rate, compared with "Normal" and "Sham". However, "Banding+SERCA" and "Banding+Parv" showed high ESP(0.1), low EDP(0.1) and fast LV relaxation rate. In "Banding", "Banding+betagal" and "Banding+saline", slope of relation between cardiac oxygen consumption and systolic pressure-volume area, O(2) cost of total mechanical energy, was twice higher than normal value, whereas slope in "Baning+SERCA" and "Banding+Parv" was similar to normal value. Furthermore, O(2) cost of LV contractility in the 3 control banding groups was approximately 3 times higher than normal value, whereas O(2) cost of contractility in "Banding+SERCA", "Banding+AAV.SERCA" and "Banding+Parv" was as low as normal value. Thus, high O(2) costs of total mechanical energy and of LV contractility in failing hearts indicate energy wasting both in chemomechanical energy transduction and in calcium handling. Improved calcium handling by both short- and long-term overexpression of SERCA2a and parvalbumin transforms the inefficient energy utilization into a more efficient state. Therefore enhancement of calcium handling either by resequestration into the SR or by intracellular buffering improves not only mechanical but energetic function in failing hearts.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Sakata S,Lebeche D,Sakata N,Sakata Y,Chemaly ER,Liang LF,Tsuji T,Takewa Y,del Monte F,Peluso R,Zsebo K,Jeong D,Park WJ,Kawase Y,Hajjar RJ

doi

10.1016/j.yjmcc.2007.01.003

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

852-61

issue

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(07)00005-3

journal_volume

pub_type

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Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins.