Cellular Prion Protein Is Essential for Myocardial Regeneration but Not the Recovery of Left Ventricular Function from Apical Ballooning

Abstract

This study tested the hypothesis that cellular prion protein (PrPC) played an essential role in myocardial regeneration and recovery of left ventricular ejection fraction (LVEF) from apical takotsubo cardiomyopathy (TCM) induced by transaortic constriction (TAC). In vitro study was categorized into G1 (H9C2), G2 (H9C2-overexpression-PrPC), G3 (H9C2-overexpression-PrPC + Stelazine/1 uM), and G4 (H9C2 + siRNA-PrPC), respectively. The results showed that the protein expressions of PrPC, cell-stress signaling (p-PI3K/p-Akt/p-m-TOR) and signal transduction pathway for cell proliferation/division (RAS/c-RAF/p-MEK/p-ERK1/2) were lowest in G1, highest in G2, significantly higher in G3 than in G4 (all p p C/p-PI3K/p-Akt/p-m-TOR/cyclin D/cyclin E and cellular-proliferation biomarkers (Ki67/PCNA/BrdU) exhibited an opposite pattern of LVEF (all p p C participated in regulating the intrinsic response of cell-stress signaling and myocardial regeneration but did not offer significant benefit on recovery of the heart function in the setting of TCM.

Keywords

• takotsubo cardiomyopathy
• cellular prion protein
• Stelazine
• cell stress