國家衛生研究院 NHRI:Item 3990099045/7959

NHRI > Institute of Biomedical Engineering and Nanomedicine > Kurt Ming-Chao Lin > Conference Papers/Meeting Abstract > Item 3990099045/7959

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/7959

Title:	Transgenic expression of Heat Shock Protein 60 results in neonatal death and adult heart failure
Authors:	Liu, SW;Chen, TH;Chen, YL;Chen, MR;Hsu, CH;Lin, KM
Contributors:	Division of Medical Engineering Research
Abstract:	Heat shock proteins (HSPs) are known for their enhanced expression and pro-survival role in cells under noxious stress. Only recently was it discovered that aberrant expression of HSPs was linked to the onset of cardiovascular diseases. HSP60, originally identified as one of the mitochondrial chaperonins, was shown involved in autoimmune, metabolic, and cardiovascular diseases, but the roles of HSP60 remain unclear in part due to the lack of HSP60 transgenic mouse models. This study aims to investigate the outcome of expressing HSP60 in cardiac tissues to elucidate the role of HSP60 in initiating apoptotic cardiomyopathy. By using a conditional HSP60 transgenic mouse line (G-Lox-HSP60) and a Cre mouse line, human HSP60 expression in most mouse tissues, driven by the ubiquitous CAG promoter, was achieved. The ubiquitous expression of HSP60 was found to cause neonatal death during postnatal day one. In HSP60 expressing newborn mice, hemorrhagic cardiac myopathy was found, and some of these mice exhibited atrium septal defects. A greatly increased rate of apoptosis was found in cardiac tissues with HSP60 overexpression, suggesting a pro-apoptotic role for HSP60. A tamoxifen-inducible Cre mouse (Myh6-Cre/ESR) was used to induce HSP60 expression in the adult mouse heart, and the results showed that dilated heart failure developed within 8 weeks after the induction of HSP60 expression. By employing an isolated perfusion model, the basal contractility was found to be significantly enhanced by HSP60, and a cardiac protection against simulated ischemia and reperfusion injury was found in mice with the HSP60 induction for 4 weeks. Both increased contractility and cardiac protection were lost in mice 6 to 8 weeks after HSP60 induction. Our results showed that HSP60 expression led to heart failure in neonatal mice and likely involved developmental defects and induced apoptosis. While expressing HSP60 in adult cardiac tissues only temporally improved cardiac function and exerted cardiac stress protection, hypertrophy and heart failure eventually occured in these mice. The G-Lox-HSP60 model that achieves expression of HSP60 in an inducible and tissue-specific manner will be useful in studies to investigate the roles and molecular details of HSP60 in various diseases.
Date:	2013-08
Relation:	Circulation Research. 2013 Aug;113(4):Abstract number 092.
Link to:	https://www.ahajournals.org/doi/10.1161/res.113.suppl_1.A092
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0009-7330&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000332063200089
Appears in Collections:	[Kurt Ming-Chao Lin] Conference Papers/Meeting Abstract

Files in This Item:

File	Description	Size	Format
ISI000332063200089.pdf		43Kb	Adobe PDF	599	View/Open

Loading...