Abstract 301: Deletion of Sam68 Attenuates Myocardial Hypertrophy
The Src-associated in mitosis 68 kDa (Sam68) belongs to the STAR (signal transducer and activator of RNA) family of RNA-binding proteins and has recently been shown to regulate angiotensin II (Ang II) signaling in vascular smooth muscle cells. In this study, we investigated the role of Sam68 in cardiac hypertrophy. Wild-type (WT) and Sam68 knockout (KO) mice were administered continuously with Ang II for 14 days via osmotic minipumps. Echocardiography analyses reveled that basal left-ventricular posterior wall thicknesses (LVPTs and LVPTd) and basal chamber sizes (LVIDs and LVIDd) are similar between the 2 groups of mice, that Ang II induced a significant elevation in LVPTs and LVPTd and reduction in LVIDs and LVIDd in both groups of mice, and that the changes of all these hypertrophic parameters were significantly attenuated in Sam68 KO than in WT mice (p<0.05 at day 14, n=15). The increase in the heart weight (HW) / body weight (BW) ratio was also lesser in Sam68 KO mice than in WT mice (p<0.05 at day 14, n=15). Then, we performed transverse aortic constriction (TAC) model. Echocardiography analyses confirmed significantly lower levels of LVPTs/d and LVIDs/d in Sam68 KO mice than in WT mice (LVPTs/d: p<0.05 at weeks 2 and 4, p<0.01 at weeks 8; LVIDs/d: p<0.05 at weeks 2, 4, and 8; n=12), however, left ventricular ejection fraction (LV EF) remained not significantly different at all these time points between the 2 groups. Histological analyses of fibrosis by Masson’s trichrome staining demonstrated a ~ 2-fold less in collagen deposition areas in Sam68 KO than in WT mice (p<0.05 at weeks 8, n=12). The attenuated hypertrophic responses of Sam68 KO mice to both Ang II treatment and TAC surgery was further supported by a lower expression of fetal genes, including β-myosin heavy chain, atrial and brain natriuretic peptides in the heart of Sam68 KO mice than in WT mice (qRT-PCR). Collectively, our results suggest that Sam68 may modulate the cause of cardiac hypertrophy
Author Disclosures: J. Zhou: None C. Boriboun: None D. Biyashev: None G. Qin: None.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2014 by American Heart Association, Inc.