The Impact of Lrat on Cardiomyocyte Energetics and Survival

• Applicant: Dr. Christian Riehle
• Subject Area: Cardiology, Angiology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 414169410

Heart failure is a major cause of death in industrialized nations and exceeds the mortality of most types of cancers with about half of patients dying within 5 years of the initial diagnosis. Furthermore, the incidence of type 2 diabetes is increasing at an alarming rate. Type 2 diabetes is characterized by insulin resistance and initial hyperinsulinemia, which accelerate the onset of heart failure. Previous studies reported perturbed vitamin A metabolism in type 2 diabetic patients. Furthermore, our preliminary data indicate a cardioprotective role for lecithin:retinol acyltransferase (Lrat), which mediates the storage of vitamin A metabolites (retinoids). Similar to Lrat, stimulated by retinoic acid 6 (Stra6) plays a central role in retinoid homeostasis and mediates intracellular uptake of retinol. However, detailed analysis of the impact of Lrat and Stra6 on cardiac energetics and the development of heart failure is lacking and will be evaluated in this proposal. Together, these studies will provide new insight into cardiac retinoid metabolism and will identify novel, retinoid-mediated cardioprotective mechanisms.

• DFG Programme: Research Grants