Mitigation of myocardial fibrosis by molecular cardiac surgery-mediated gene overexpression

The Journal of Thoracic and Cardiovascular Surgery
Michael G KatzCharles R Bridges

Abstract

Heart failure is accompanied by up-regulation of transforming growth factor beta signaling, accumulation of collagen and dysregulation of sarcoplasmic reticulum calcium adenosine triphosphatase cardiac isoform 2a (SERCA2a). We examined the fibrotic response in small and large myocardial infarct, and the effect of overexpression of the SERCA2a gene. Ischemic cardiomyopathy was induced via creation of large or small infarct in 26 sheep. Animals were divided into 4 groups: small infarct; large infarct with heart failure; gene-treated (large infarct with heart failure followed by adeno-associated viral vector, serotype 1.SERCA2a gene construct transfer by molecular cardiac surgery with recirculating delivery); and control. Heart failure was significantly less pronounced in the gene-treated and small-infarct groups than in the large-infarct group. Expression of transforming growth factor beta signaling components was significantly higher in the large-infarct group, compared with the small-infarct and gene-treated groups. Both the angiotensin II type 1 receptor and angiotensin II were significantly elevated in the small- and large-infarct groups, whereas gene treatment diminished this effect. Active fibrosis with de novo collagen syn...Continue Reading

Citations

Feb 9, 2017·Current Opinion in Cardiology·Kyle ChamberlainThomas Weber
Jul 21, 2017·Human Gene Therapy. Clinical Development·Michael G KatzCharles R Bridges
Feb 6, 2017·Cardiovascular Research·Elizabeth MurphyJunhui Sun
Jan 7, 2017·Circulation Research·Roger J Hajjar, Kiyotake Ishikawa
Oct 26, 2018·Circulation Research·Kiyotake IshikawaRoger J Hajjar
Oct 30, 2018·Journal of the American Heart Association·Lukas J MotlochFadi G Akar
Nov 5, 2019·The Journal of Thoracic and Cardiovascular Surgery·Michael G KatzAnthony S Fargnoli
Feb 17, 2019·Journal of Molecular and Cellular Cardiology·Jae Gyun OhDongtak Jeong

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