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

Jiunn Jye Sheu, Han Tan Chai, John Y. Chiang, Pei Hsun Sung, Yi Ling Chen, Hon Kan Yip*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

4 Scopus citations

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 < 0.001). Adult-male B6 mice (n = 30) were equally categorized in group 1 (sham-control), group 2 (TAC) for 14 days, then relieved the knot and administered BrdU (50 ug/kg/intravenously/q.6.h for two times from day-14 after TAC) and group 3 (TAC + Stelazine/20 mg/kg/day since day 7 after TAC up to day 21 + BrdU administered as group 2), and animals were euthanized at day 28. The results showed that by day 28, the LVEF was significantly higher in group 1 than in groups 2/3 and significantly higher in group 3 than in group 2, whereas the LV chamber size exhibited an opposite pattern of LVEF (all p < 0.0001). The protein expressions of PrPC /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 < 0.0001) among the three groups, whereas the protein expressions of RAS/c-RAF/p-MEK/p-ERK1/2 were significantly and progressively increased from groups 1 to 3 (all p < 0.0001). In conclusion, PrPC 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.

Original languageEnglish
Article number167
JournalBiomedicines
Volume10
Issue number1
DOIs
StatePublished - 01 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Cell stress
  • Cellular prion protein
  • Stelazine
  • Takotsubo cardiomyopathy

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