Myocardin ablation in a cardiac-renal rat model. View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Anupam Mittal, Santanu Rana, Rajni Sharma, Akhilesh Kumar, Rishikesh Prasad, Satish K Raut, Sagartirtha Sarkar, Uma Nahar Saikia, Ajay Bahl, Perundurai S Dhandapany, Madhu Khullar

ABSTRACT

Cardiorenal syndrome is defined by primary heart failure conditions influencing or leading to renal injury or dysfunction. Dilated cardiomyopathy (DCM) is a major co-existing form of heart failure (HF) with renal diseases. Myocardin (MYOCD), a cardiac-specific co-activator of serum response factor (SRF), is increased in DCM porcine and patient cardiac tissues and plays a crucial role in the pathophysiology of DCM. Inhibiting the increased MYOCD has shown to be partially rescuing the DCM phenotype in porcine model. However, expression levels of MYOCD in the cardiac tissues of the cardiorenal syndromic patients and the effect of inhibiting MYOCD in a cardiorenal syndrome model remains to be explored. Here, we analyzed the expression levels of MYOCD in the DCM patients with and without renal diseases. We also explored, whether cardiac specific silencing of MYOCD expression could ameliorate the cardiac remodeling and improve cardiac function in a renal artery ligated rat model (RAL). We observed an increase in MYOCD levels in the endomyocardial biopsies of DCM patients associated with renal failure compared to DCM alone. Silencing of MYOCD in RAL rats by a cardiac homing peptide conjugated MYOCD siRNA resulted in attenuation of cardiac hypertrophy, fibrosis and restoration of the left ventricular functions. Our data suggest hyper-activation of MYOCD in the pathogenesis of the cardiorenal failure cases. Also, MYOCD silencing showed beneficial effects by rescuing cardiac hypertrophy, fibrosis, size and function in a cardiorenal rat model. More... »

PAGES

5872

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-42009-z

DOI

http://dx.doi.org/10.1038/s41598-019-42009-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113355955

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30971740


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