Myocardin ablation in a cardiac-renal rat model

• Published in: Scientific reports 2019-04, Vol.9 (1), p.5872-5872, Article 5872
• Main Authors: Mittal, Anupam, Rana, Santanu, Sharma, Rajni, Kumar, Akhilesh, Prasad, Rishikesh, Raut, Satish K., Sarkar, Sagartirtha, Saikia, Uma Nahar, Bahl, Ajay, Dhandapany, Perundurai S., Khullar, Madhu
• Format: Article
• Language: English
• Subjects: 13; 13/51; 14; 38; 38/109; 38/89; 38/90; 42; 631/1647/2017/2003; 64; 692/4019/592; Angiotensin II - pharmacology; Animals; Cardio-Renal Syndrome - metabolism; Cardio-Renal Syndrome - pathology; Cardiomyopathy; Cardiomyopathy, Dilated - metabolism; Cardiomyopathy, Dilated - pathology; Collagen Type I - genetics; Collagen Type I - metabolism; Congestive heart failure; Dilated cardiomyopathy; Disease Models, Animal; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibrosis; Heart failure; Heart Ventricles - pathology; Humanities and Social Sciences; Hypertrophy; Kidney diseases; Male; multidisciplinary; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Nuclear Proteins - antagonists & inhibitors; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Pathogenesis; Phenotypes; Rats; Renal artery; Renal failure; Renal function; RNA Interference; RNA, Small Interfering - metabolism; Rodents; Science; Science (multidisciplinary); Serum response factor; siRNA; Trans-Activators - antagonists & inhibitors; Trans-Activators - genetics; Trans-Activators - metabolism; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Ventricle; Ventricular Function
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-42009-z

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.