Abstract 375: Myocardin Induces Cardiac Hypertrophy in vivo
Myocardin (Myoc) is a transcriptional coactivator of the serum response factor that transactivates cardiac and smooth muscle genes. Recently, it has been observed that Myoc promotes cardiac hypertrophy in cultured neonatal cardiomyocytes. However, the role of this protein in the whole adult heart remains unclear.
Objective: to determinate the effect of Myoc on cardiac hypertrophy promotion in both normal and hypertensive rats.
Methods: normotensive (Nt) or hypertensive (2 kidneys-1clip Goldblatt model for 10 days; Gb) male adult Sprague Dawley rats were treated by cardiac gene transfer with an adenovirus containing the complete sequence of Myoc (AdMyoc) or with an adenovirus without the specific insert (AdCont). Ten days after the infection a 2-D echocardiographic evaluation was performed and the animals were sacrificed.
Results: in the Nt-AdMyoc rats (n= 13) a 23% increase in relative ventricular mass (RVM) was observed compared to Nt-AdCont rats (n= 14; p < 0.05). The RVM in Gb-AdMyoc rats (n= 7) was 36% higher than in Nt-AdCont rats (p < 0.05). RVM was similar in both Gb-AdCont (n= 7) and Nt-AdMyoc rats. Morphometric analysis showed a significant (p < 0.05) increase of 52, 57% and 73% in the cardiomyocyte area, in the Nt-AdMyoc, Gb-AdCont and Gb-AdMyoc rats, respectively, compared to Nt-AdCont rats. In the Nt-AdMyoc animals the echocardiographic analysis showed significant interventricular septum thickness increase by 10% compared to Nt-AdCont rats (p< 0.05). The Gb-AdMyoc group showed an 11% increase in the interventricular septum thickness compared both with Nt-AdCont and with Gb-AdCont rats (p< 0.05). No signs of ventricular dysfunction were observed in any group. No differences were observed by Western blot in the cardiac expression of alpha-actin neither of beta-MHC. Cardiac cell proliferation (assessed by immunostaining of Ki-67) and interstitial collagen volume fraction were similar in all groups.
Discussion: our findings are consistent with the capability of Myoc to induce in vivo cardiac hypertrophy in the adult rat. This effect is synergistically potentiated in renin dependent hypertension, and does not seem to include myocardial fibrosis neither cardiac dysfunction. Fondecyt 1040832, 1030181.