SummaryMyocardin is a remarkably potent transcriptional coactivator expressed specifically in cardiac muscle lineages and smooth muscle cells during postnatal development. Myocardin shares homology with myocardin-related transcription factor-A (MRTF-A), which are expressed in a broad range of embryonic and adult tissues. Our previous results show that myocardin induces cardiac hypertrophy. However, the effects of MRTF-A in cardiac hypertrophy remain poorly understood. Our present work further demonstrates that myocardin plays an important role in inducing hypertrophy. At the same time, we find that overexpression of MRTF-A in neonatal rat cardiomyocytes might induce cardiomyocyte hypertrophy. Furthermore, MRTF-A expression is induced in phenylephrine, angiotensin-II, and transforming growth factor-b-stimulated cardiac hypertrophy, whereas a dominant-negative form of MRTF-A or MRTF-A siRNA strongly inhibited upregulation of hypertrophy genes in response to hypertrophic agonists in neonatal rat cardiomyocytes. Our studies indicate that besides myocardin, MRTF-A might play an important role in cardiac hypertrophy. Our findings provide novel evidence for the future studies to explore the roles of MRTFs in cardiac hypertrophy.
The long‐term failure of vein grafts due to neointimal hyperplasia remains a difficult problem in cardiovascular surgery. Exploring novel approaches to prevent neointimal hyperplasia is important. MicroRNA‐146a (miR‐146a) plays an essential role in promoting vascular smooth muscle cell (VSMC) proliferation. Thus, the aim of the present study is to investigate whether adenovirus‐mediated miR‐146a sponge (Ad‐miR‐146a‐SP) gene therapy could attenuate neointimal formation in rat vein grafts. (Ad‐miR‐146a‐SP) was constructed to transfect cultured VSMCs and grafted veins. To improve the efficiency of transferring the miR‐146a sponge gene into the grafted veins, 20% poloxamer F‐127 gel incorporated with 0.25% trypsin was used to increase adenovirus contact time and penetration. miR‐146a‐SP transduction significantly reduced the expression of miR‐146a both in cultured VSMCs and vein grafts. miR‐146a sponge markedly attenuated VSMC proliferation and migration. Consistent with this, miR‐146a sponge gene therapy significantly attenuated neointimal formation and also improved blood flow in the vein grafts. Mechanistically, we identified the Krüppel‐like factor 4(KLF4) as a potential downstream target gene of miR‐146a in vein grafts. Our data show that miR‐146a sponge gene therapy could effectively reduce miR‐146a activity and attenuate neointimal formation in vein grafts, suggesting its potential therapeutic application for prevention of vein graft failure. © 2018 IUBMB Life, 71(1):125–133, 2019
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