Proteomics Analysis of Cardiac Extracellular Matrix Remodeling in a Porcine Model of Ischemia-Reperfusion Injury
Background—Following myocardial ischemia, extracellular matrix (ECM) deposition occurs at the site of the focal injury and at the border region.
Methods and Results—We have applied a novel proteomic method for the analysis of ECM in cardiovascular tissues to a porcine model of ischemia-reperfusion injury. ECM proteins were sequentially extracted and identified by liquid chromatography tandem mass spectrometry. For the first time, ECM proteins, such as cartilage intermediate layer protein 1 (CILP-1), matrilin-4, extracellular adipocyte enhancer binding protein 1 (AEBP-1), collagen alpha-1 (XIV) and several members of the small leucine-rich proteoglycan family, including asporin and prolargin, were shown to contribute to cardiac remodeling. A comparison in two distinct cardiac regions (the focal injury in the left ventricle and the border region close to the occluded coronary artery) revealed a discordant regulation of protein and messenger RNA levels: while gene expression for selected ECM proteins was similar in both regions, the corresponding protein levels were much higher in the focal lesion. Further analysis based on more than hundred ECM proteins delineated a signature of early and late stage cardiac remodelling with transforming growth factor beta 1 (TGFβ-1) signalling being at the centre of the interaction network. Finally, novel cardiac ECM proteins identified by proteomics were validated in human left ventricular tissue acquired from ischemic cardiomyopathy patients at cardiac transplantation.
Conclusions—Our findings reveal a bio-signature of early and late stage ECM remodeling after myocardial ischemia-reperfusion injury, which may have clinical utility as prognostic markers and modifiable targets for drug discovery.
- Received July 19, 2011.
- Accepted December 12, 2011.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited