Locally expressed IGF1 propeptide improves mouse heart function in induced dilated cardiomyopathy by blocking myocardial fibrosis and SRF-dependent CTGF induction.

Disease Models & Mechanisms
Melissa TouvronJean-François Decaux

Abstract

Cardiac fibrosis is critically involved in the adverse remodeling accompanying dilated cardiomyopathies (DCMs), which leads to cardiac dysfunction and heart failure (HF). Connective tissue growth factor (CTGF), a profibrotic cytokine, plays a key role in this deleterious process. Some beneficial effects of IGF1 on cardiomyopathy have been described, but its potential role in improving DCM is less well characterized. We investigated the consequences of expressing a cardiac-specific transgene encoding locally acting IGF1 propeptide (muscle-produced IGF1; mIGF1) on disease progression in a mouse model of DCM [cardiac-specific and inducible serum response factor (SRF) gene disruption] that mimics some forms of human DCM. Cardiac-specific mIGF1 expression substantially extended the lifespan of SRF mutant mice, markedly improved cardiac functions, and delayed both DCM and HF. These protective effects were accompanied by an overall improvement in cardiomyocyte architecture and a massive reduction of myocardial fibrosis with a concomitant amelioration of inflammation. At least some of the beneficial effects of mIGF1 transgene expression were due to mIGF1 counteracting the strong increase in CTGF expression within cardiomyocytes caused ...Continue Reading

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Citations

Jun 19, 2013·Journal of Cardiovascular Translational Research·Enrique Lara-PezziPablo García-Pavía
Jun 19, 2013·Cardiovascular Research·Hadhami HamdiOnnik Agbulut
Oct 16, 2012·American Journal of Physiology. Heart and Circulatory Physiology·P ZhangU Mende
Aug 10, 2013·Disease Models & Mechanisms·Jonas LexowNadia Rosenthal
Sep 24, 2015·Journal of Molecular and Cellular Cardiology·Anita OngherthSusanne Lutz
Sep 17, 2013·Biochimica Et Biophysica Acta·Ellen DirkxLeon J De Windt
Jun 12, 2016·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Ferenc BoldizsarTibor A Rauch
Oct 13, 2015·PloS One·Sundaravadivel BalasubramanianDhandapani Kuppuswamy
Sep 7, 2017·GeroScience·Zoltan UngvariAnna Csiszar
Aug 18, 2018·Journal of Biomedical Science·Jianquan ZhaoLongke Ran
Jan 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aude AngeliniJean-Francois Decaux

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Methods Mentioned

BETA
electron microscopy
PCR
Confocal microscopy
transgenic

Software Mentioned

Primer3
ImageJ

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