Life Sciences & Biotechnology
Title : | study on the mechanistic insight towards nitroxidative stress mediated transition from physiological to pathological cardiac hypertrophy in a preclinical model |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Hypertrophic cardiomyopathy |
Principal Investigator : | Prof. sagartirtha sarkar, University of Calcutta, Kolkata, West Bengal |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | sagartirtha.sarkar@gmail.com |
Details
Executive Summary : | The regimented exercise induced physiological adaptations are lost during exercise withdrawal along with manifestation of cardiac pathophysiology leading to deterioration of the cardiac function. This area of cardiac disease biology is yet a lesser explored area. The oxidative load regulation in the myocardium of regimented exercising and exercise withdrawal groups has not been addressed ever. Our initial data suggest that reactive oxygen species sharply increases after withdrawal from regimented exercise during the manifestation of pathological cardiac hypertrophy where PKC isoform switching from PKCalpha to PKCδ is evident. At the same time, nitric oxide load remains elevated in both conditions which leads to a hypothesis that the nitroxidative load (viz the cumulative effects of NO and ROs) regulators play a key role in underlining the manifestation of the cardiac pathophysiology without any external stimulus and PKC isoform switching might underline this nitroxidative load regulation in both conditions. This proposal is therefore designed to decipher the role of nitroxidative stress in modulating cardiac pathophysiology via novel cardiac targeted therapeutic platform to enable cardiomyocyte-specific release of siRNAs in animal model of regimented exercise and exercise withdrawal abating any bystander effects on other vital organs of the body. The influence of such nitroxidative stress towards alterations of the molecular regulators of cardiac metabolism will also be studied in this project. Finally, Arjunolic acid will be delivered to the diseased heart by the novel myocardium targeted nanovehicle platform that could be developed as a new targeted therapeutics to combat exercise withdrawal related cardiac pathophysiology and heart failure in future. |
Total Budget (INR): | 49,60,000 |
Organizations involved