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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/2704

Title: Left ventricular mechanical and energetic changes in long-term isoproterenol-induced hypertrophied hearts of SERCA2a transgenic rats.
Other Titles: SERCA2a過剰発現ラットにおけるイソプロテレノール持続投与誘導肥大心の左室力学的エネルギー学的性質の変化
Authors: Mitsuyama, Shinichi
Takeshita, Daisuke
Obata, Koji
Zhang, Guo-Xing
Takaki, Miyako
Keywords: Heart failure
Ca2 + handling
Oxygen consumption
Excitation–contraction coupling
Issue Date: Jun-2013
Publisher: Academic Press / Elsevier
Citation: Journal of molecular and cellular cardiology Vol.59 p.95-106
Abstract: Overexpression of cardiac sarcoplasmic reticulum Ca2 +-ATPase (SERCA2a) has been suggested as a strategic intervention for cardiac failure. However, its benefit in wild-type (WT) rats with normal SERCA2a levels seems to be small. To investigate whether it would be beneficial in a cardiac failure model with down-regulated SERCA2a levels, we made a cardiac hypertrophy model using isoproterenol infusion (1.2 mg kg− 1 day− 1 for 1 or 4 weeks; TG-ISO1w and TG-ISO4w, respectively) in SERCA2a transgenic (TG) rats and compared these rats with littermate WT rats that underwent the same treatments (WT-ISO1w and WT-ISO4w). We analyzed the left ventricular (LV) mechanoenergetics in the excised heart using our original cross-circulation system. The downward shift of curvilinear LV end-systolic pressure–volume relations (ESPVRs) observed in WT-ISO4w rats was abolished in TG-ISO4w rats. The slope and VO2 intercept of the VO2 (myocardial oxygen consumption per beat)–PVA (systolic pressure–volume area: total mechanical energy per beat) linear relation did not differ in any of the groups. The most important finding was a significantly smaller O2 cost of LV contractility in the TG-ISO4w group, which means that less O2 is needed to exert the same LV contractility, compared with the other groups. The increased ratio of SERCA2a/phospholamban returned to the level of the WT-control group only in the TG-ISO4w group. Longer-term up-regulation of mitochondrial transcription factor A for genes of mitochondrial enzymes producing ATP was observed in TG rats. In conclusion, longer-term overexpression of SERCA2a will be beneficial in the present cardiac failure model with down-regulated SERCA2a levels.
Description: 博士(医学)・甲619号・平成26年3月17日
URI: http://hdl.handle.net/10564/2704
ISSN: 00222828
Academic Degrees and number: 24601A619
Degree-granting date: 2014-03-17
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2013年度

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