Abstract 14967: The Ptip-Associated Histone Methyltransferase Complex is Necessary for the Development of Compensated Cardiac Hypertrophy
PTIP is a key component of a histone methyltransferase (HMT) complex that regulates H3K4me3 marks at the 5’ region of actively expressed genes. We hypothesized that the PTIP-HMT complex is necessary for the upregulation of genes that regulate cardiac hypertrophy. Using a tamoxifen inducible αMHC-Cre murine model and a floxed allele of PTIP, we generated inducible PTIP null mice (PTIP-) and control mice (PTIP+). In order to test the importance of the PTIP-HMT in the development of cardiac hypertrophy, PTIP+ and PTIP- mice were subjected to 2wk of transverse aortic constriction (TAC) or sham surgery (Sham). PTIP- TAC and PTIP+TAC hearts demonstrated similar amounts of cardiac hypertrophy as compared to PTIP+ Sham and PTIP- Sham hearts (Table 1). H&E staining of ventricular cross sections revealed that PTIP-TAC hearts are dilated when compared to PTIP+TAC hearts (Figure1). Echocardiography revealed that PTIP-TAC mice develop a significant increase in LVEDD and a significant decrease in EF when compared with PTIP- Sham and PTIP+TAC mice (Table 1). Picrosirius red staining revealed that PTIP-TAC hearts have more cardiac fibrosis than PTIP+TAC hearts (Table 1). Gene expression array of LV tissue revealed a total of 331 genes that were upregulated in PTIP+TAC as compared to PTIP-TAC mice. Among these genes were members of the PI3K family, integrins, the phosphodiesterase family, voltage dependent calcium channels, voltage gated sodium channels and inward rectifying potassium channels. In conclusion, the PTIP-HMT complex is necessary for the development of compensated cardiac hypertrophy, and the absence of this complex results in cardiac dilatation, fibrosis, and early failure.
- © 2013 by American Heart Association, Inc.