Abstract 11432: Selective Blockade of Periostin 1 Decreased Infarct Size and Preserved Cardiac Performance in Rat Acute Myocardial Infarction
Objectives The purpose of this study was to clarify the role of the splicing isoforms of periostin in myocardial infarction (MI) using a rat experimental MI model.
Background Our previous report demonstrated that over-expression of full-length periostin (periostin1) resulted in ventricular dilation with enhanced interstitial collagen. Consistently, another study documented improved ventricular hypertrophy and remodeling in periostin knockout mice following MI. However, there is another report showing cardiac repair through cardiomyocyte proliferation and angiogenesis promoted by periostin lacking exon17-coded structure (periostin2). Thus, we focused on the functional difference between splicing isoforms of periostin; hypothesizing different isoforms could play different roles in MI.
Methods The present study employed a neutralizing antibody against exon17 to inhibit periostin1 selectively (Pn1Ab). Rats were subjected to coronary ligation prior to Pn1Ab injection, and analyzed physiologically and immunohistochemically for evaluation of cardiac performance, infarct size and fibrotic response. In vitro study, initially we analyzed gene expression of each periostin splicing isoform and fibrosis-related molecules in rat fibroblasts stimulated with TGF-β1. Secondly, we evaluated the effect of Pn1Ab on fibrotic process.
Results Administration of Pn1Ab resulted in 24.1 % decrease in infarct size and 38.2 % decrease in fibrotic area at 8 weeks post-MI (n=21, P<0.05). Consistently, echocardiography demonstrated 26.3 % better ejection fraction (P<0.05), and left ventricular end-diastolic pressure (LVEDP) rise as well as plasma brain natriuretic peptide (BNP) level was dramatically curbed (P<0.05). Inhibition of fibrosis was associated with suppressed fibrosis-related gene expression. Importantly, the number of myofibroblasts was significantly reduced in the Pn1Ab group, while neither cardiomyocyte proliferation nor angiogenesis was detected. It was also confirmed that Pn1Ab prevented fibrotic response in cultured fibroblasts.
Conclusions Pn1Ab decreased infarct size through preventing fibrotic response. Specific blockade of Pn1 without Pn2 might be a therapeutic target to preserve cardiac performance in MI patients.
- © 2011 by American Heart Association, Inc.