Myocardin ablation in a cardiac-renal rat model
Autor: | Perundurai S. Dhandapany, Anupam Mittal, Uma Nahar, Rajni Sharma, Akhilesh Kumar, Madhu Khullar, Santanu Rana, Satish K. Raut, Ajay Bahl, Sagartirtha Sarkar, Rishikesh Prasad |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male Cardiomyopathy lcsh:Medicine 030204 cardiovascular system & hematology Pathogenesis 0302 clinical medicine Fibrosis Transforming Growth Factor beta Medicine Ventricular Function Myocytes Cardiac RNA Small Interfering lcsh:Science 0303 health sciences Multidisciplinary Angiotensin II Nuclear Proteins Dilated cardiomyopathy 3. Good health Cardiology cardiovascular system RNA Interference Cardiac function curve Cardiomyopathy Dilated medicine.medical_specialty Heart Ventricles Cardiorenal syndrome Collagen Type I Article 03 medical and health sciences Internal medicine medicine.artery Animals Renal artery 030304 developmental biology Cardio-Renal Syndrome business.industry lcsh:R Fibroblasts medicine.disease Rats Collagen Type I alpha 1 Chain Disease Models Animal 030104 developmental biology Myocardin Heart failure Trans-Activators lcsh:Q business 030217 neurology & neurosurgery |
Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019) |
ISSN: | 2045-2322 |
Popis: | 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 mice 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 mice phenotype. However, expression levels of MYOCD in the cardiac tissues of the cardiorenal syndromic patients and the beneficial 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. |
Databáze: | OpenAIRE |
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