PS 04-20 SELECTIVE BLOCKADE OF PERIOSTIN EXON-17 IMPROVES CARDIAC PERFORMANCE IN RAT MYOCARDIAL ISCHEMIA MODEL

    loading  Checking for direct PDF access through Ovid

Abstract

Objective:

Although mortality rate due to acute myocardial infarction (AMI) has been extremely improved by the development of early reperfusion therapy, the sudden death due to acute heart failure, lethal arrhythmias, and chronic heart failure post AMI are still clinically important issue. We previously reported that periostin expression significantly increased mainly in myofibroblast following AMI and over-expression of full length of periostin (Pn variant 1) resulted in ventricular dilation with enhanced interstitial collagen deposition in rat model. However, other reports documented that short form splicing variants, Pn variant 2 (lacking exon-17) or Pn variant 4 (lacking exon-17 and -21), promoted cardiac repair by angiogenesis or preventing cardiac rupture following AMI.

Design and Method:

Therefore, we employed neutralizing antibody (PnAb) that selectively inhibit Pn variant 1 by blockade of exon-17 and tested in rat AMI model.

Results:

Administration of PnAb resulted in a significant decrease in infarcted and fibrotic area of myocardium and preserved ejection fraction and preventing wall thinning and elevation of LVEDP at 2 months. Strikingly, PnAb significantly increased residual myocytes area in ischemic region. Moreover, the level of Pn 1 expression at day 7 was correlated significantly with the severity of AMI. In vitro study demonstrated that Pn 1, but not Pn 2 or 4, inhibited fibroblast and myocyte attachment and caused myocyte apoptosis, which might account for cell slippage observed during cardiac remodeling.

Conclusions:

In summary, Pn variant 1 expression significantly increased during cardiac remodeling, and inhibited anchorage- dependent myocyte growth and survival. Specific neutralizing antibody against Pn exon-17, Pn variant 1, without suppressing other Pn variants significantly suppressed cardiac remodeling post AMI and might offer a new class of medication for the treatment of AMI patients.

Related Topics

    loading  Loading Related Articles