Abstract 287: Chamber Specific Function of p38 MAP Kinases in Right Ventricle Development, Hypertrophy, and Dysfunction
Background: Postnatal heart maturation is a well orchestrated process involving chamber specific changes in myocyte proliferation and growth. While the left ventricle undergoes significant growth, the right ventricle regresses relative to the left in terms of both myocyte number and size. While much attention has been focused on the left ventricular myocyte proliferation and hypertrophy, right ventricle specific changes are poorly studied. p38 MAP kinase is a well established signaling pathway for stress response and also plays an important role in cell differentiation, viability and proliferation. Its role in chamber specific postnatal heart maturation, however, has not been demonstrated
Results and Methods: We observed RV specific induction of myocyte apoptosis and suppression of myocyte proliferation in neonatal hearts, coinciding with a transient induction of p38 activity significantly higher in the RV relative to the LV at P3 and P7 wild-type mouse hearts. In cardiomyocyte specific p38 MAP kinase alpha&beta double KO (p38ab cdKO) mice, echocardiographic and histological analyses revealed RV specific chamber enlargement and dysfunction associated with significant postnatal lethality. Apoptotic activity in the RV was suppressed at P1 and myocyte proliferation and hypertrophy were significantly elevated at P3 and P7 in the p38ab cdKO hearts compared to the wild-type. In contrast, no differences were observed in the LV between the p38ab cdKO and wild-type. Consequently, the surviving p38ab cdKO mice showed significant and RV specific enlargement and dysfunction, leading to eventual RV failure and pulmonary hypertension.
Conclusion: p38 a&b MAP kinases are essential to RV specific maturation in postnatal hearts. p38ab cdKO mice represent a unique RV-specific hypertrophy and heart failure model for further studies.
Author Disclosures: T. Yokota: None V. Ren: None Y. Wang: None.
- © 2014 by American Heart Association, Inc.