Cellular, structural and functional cardiac remodelling following pressure overload and unloading. (1st August 2016)

• Record Type: Journal Article
• Authors: Dadson, Keith; Kovacevic, Vera; Rengasamy, Palanivel; Kim, Grace Ha Eun; Boo, Stellar; Li, Ren-Ke; George, Isaac; Schulze, P. Christian; Hinz, Boris; Sweeney, Gary
• Is Part Of: International journal of cardiology. Volume 216(2016)
• Page Start: 32
• Page End: 42
• Publication Date: 2016-08-01
• Subjects: Pressure overload -- Reverse remodelling -- Fibrosis -- Extracellular matrix -- Autophagy -- Adiponectin; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2016.03.240
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: The cardiac remodelling process in advanced heart failure due to pressure overload has not been clearly defined but likely involves mechanisms of cardiac fibrosis and cardiomyocyte hypertrophy. The aim of this study was to examine pressure overload (PO)-induced cardiac remodelling processes and their reversibility after unloading in both humans with heart failure and a mouse model of PO induced by aortic constriction. Methods & Results: Speckle tracking echocardiography showed PO-induced cardiac dysfunction in mice was reversible after removal of aortic constriction to unload. Masson's Trichrome staining suggested that PO-induced myocardial fibrosis was reversible, however detailed analysis of 3-dimensional collagen architecture by scanning electron microscopy demonstrated that matrix remodelling was not completely normalised as a disorganised network of thin collagen fibres was evident. Analysis of human left ventricular biopsy samples from HF patients revealed increased presence of large collagen fibres which were greatly reduced in paired samples from the same individuals after unloading by left ventricular assist device implantation. Again, an extensive network of small collagen fibres was still clearly seen to closely surround cardiomyocytes after unloading. Other features of PO-induced remodelling including increased myofibroblast content, cardiomyocyte disarray and hypertrophy were largely reversed upon unloading in both humans and mouse model. Previous work in humans demonstrated that receptors for adiponectin, an important mediator of cardiac fibrosis and hypertrophy, decreased in heart failure patients and returned to normal after unloading. Here we provide novel data showing a similar trend for adiponectin receptor adaptor protein APPL1, but not APPL2 isoform. Conclusions: LV unloading diminishes PO-induced cardiac remodelling and improves function. These findings add new insights into the cardiac remodelling process, and provide novel targets for future pharmacologic therapies.