Abstract 19232: The Retinoblastoma Protein is Inactivated in Response to Cardiac Pressure Overload and Regulates Apoptosis and Autophagy in Cardiomyocytes

The retinoblastoma protein (pRb) is a well-known regulator of cell cycle, apoptosis and differentiation. The best studied binding partner of pRb is the E2f transcription factor family. Bound to E2fs, pRb inhibits the ability of E2fs to promote transcription. Here we investigated the role of pRb in mediating growth and death of cardiomyocytes (CMs) in vivo during pressure overload (PO). We first investigated the phosphorylation and activity status of pRb in response to PO. Transverse aortic constriction (TAC) was performed in wild type mice. Since phosphorylation of pRb at Ser780 is known to de-repress E2fs, we conducted Western blot analyses using a specific antibody against pRb phosphorylated at Ser780. TAC for 4 weeks induced a significant increase in Ser780 phosphorylation of pRb compared to sham operation. In order to elucidate the function of endogenous pRb during PO, cardiac specific pRb knockout (cRb-KO) mice were also subjected to TAC. Cardiac hypertrophy (heart weight/tibial length: 12.93 ± 0.85 vs. 9.32 ± 0.34, p 2.5 times) mRNA, well-known targets of E2f mediated transcription, at baseline and after TAC, suggesting that E2f transcription is stimulated by downregulation of endogenous pRb. cRb-KO mice exhibited an increase in TUNEL-positive nuclei (0,42% vs. 0,18%, p