A major etiology of heart failure (HF) is ischemic heart disease with attendant myocardial infarction (MI). HF is characterized by remodeling of the extracellular matrix (ECM). Periostin (POSTN) secreted by myofibroblasts, is a profibrotic matricellular protein that is known to be reexpressed in the adult heart after pathological insult. Following MI in both human and mouse heart, periostin is secreted in the infarcted adult heart between days 3 and 4 in the un-infarcted myocardium. periostin is secreted from myofibroblasts to support wound healing but also contributes to pathological cardiac hypertrophy, interstitial fibrosis, and ventricular remodeling after HF. While it is known that male mice lacking the Postn gene have a low survival rate after MI as a result of ventricular rupture, the survival rate for female mice lacking periostin has not been addressed.
Postn knockout (KO) mice were generated by homozygous knock-in of MerCreMer cDNA cassette (PostnMCM/MCM) to delete exon number 1 which encodes the signal peptide that promotes periostin secretion. The effect of the deletion was confirmed by western blotting (WB), immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR) for mRNA. Following the surgical induction of MI, the survival rate of female mice was 88% (+/- 6.5%) 3 days post-MI compared to 22.2% (+/- 9.8%) the age-matched male group (***P<0.001) by log-rank test. The deaths of these mice were associated with left ventricular rupture. Furthermore, female survival rate was 68% (+/- 9.3%) at 7 days post-MI compared to 22.2% (+/- 0.0%) in males (***P<0.001). We extended the observation of groups to 14 days (for females only) and the survival rate remained at 68% (+/- 0.0%).
For the first time, we show that female mice with Postn KO have significantly higher survival rate after MI compared to male mice. We conclude that periostin release in the myocardium is required for acute cardiac wound healing and maintenance of the integrity of the left ventricular wall after MI. There is a significantly higher dependency of periostin expression in males than in females. Further investigation is required to shed light on the mechanism of the sex-dependent differential survival rate after MI in Postn KO mice.