Ameliorated stress related proteins are associated with improved cardiac function by sarcoplasmic reticulum calcium ATPase gene transfer in heart failure
Ameliorated stress related proteins are associated with improved cardiac function by sarcoplasmic reticulum calcium ATPase gene transfer in heart failure作者机构：First Department of Geriatric Cardiology Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China Department of Geriatric Ultrasound Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China Department of Cardiac Surgery Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China
出 版 物：《Journal of Geriatric Cardiology》 (老年心脏病学杂志（英文版）)
年 卷 期：2012年第9卷第3期
页 面：269-277页
核心收录：
学科分类：0710[理学-生物学] 083001[工学-环境科学] 0830[工学-环境科学与工程（可授工学、理学、农学学位）] 07[理学] 08[工学] 071003[理学-生理学]
基 金：grants from the National Nature Science Foundation China
主 题：Heart failure Sarco-endoplasmic reticulum calcium ATPase Gene transfer Stress reaction Neuro-hormonal factors
摘 要：Background Previous studies showed that overexpression of sarco-endoplasmic retieulum calcium ATPase （SERCA2a） in a variety of heart failure （HF） models was associated with greatly enhanced cardiac performance. However, it still undefined the effect of SERCA2a overexpression on the systemic inflammatory response and neuro-hormonal factors. Methods A rapid right ventricular pacing model of experimental HF was used in beagles. Then the animals underwent recombinant adeno-associated vires 1 （rAAV1） mediated gene trans- fection by direct intra-myocardium injection. HF animals were randomized to receive the SERCA2a gene, enhanced green fluorescent protein （control） gene, or equivalent phosphate buffered saline. Thirty days after gene delivery, the cardiac function was evaluated by echocardiographic testing. The protein level of SERCA2a was measured by western blotting. The proteomic analysis of left ventricular （LV） sample was determined using two-dimensional （2-D） gel el^ctrophoresis and MALDI-TOF-MS. The serum levels of the systemic inflammatory and neuro-hormonal factors were assayed using radioimmunoassay kits. Results The cardiac function improved after SERCA- 2a gene transfer due to the significantly increased SERCA2a protein level. Beagles treated with SERCA2a had significantly decreased serum levels of the inflammatory markers （interleukin-6 and tumor necrosis factor-a） and neuro-hormonal factors （brain natriuretic peptide, endothelin-1 and angiotensin II） compared with HF animals. The myocardial proteomic analysis showed that haptoglobin heavy chain, heat shock protein （alpha-crystallin-related, B6） were down-regulated, and galectin-1 was up-regulated in SERCA2a group compared with HF group, companied by up-regulated contractile proteins and NADH dehydrogenase. Conclusions These findings demonstrate that regional intramyocardial injections of rAAV 1-SERCA2a vectors may improve global LV function, correlating with reverse activation of the systemic inflammatory,
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