GSE202418: Retinol Dehydrogenase 10 Reduction Mediated Retinol Metabolism Disorder Promotes Diabetic Cardiomyopathy

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Description

Submission Date: May 06, 2022

Summary: Diabetic cardiomyopathy (DCM) is a primary myocardial injury induced by diabetes mellitus (DM) with a complex pathogenesis. In this study, we identified disordered cardiac retinol metabolism in T2DM mice and patients characterized by retinol (vitamin A, Rol) overload, all-trans retinoic acid (atRA) deficiency and retinoic acid receptors (RARs) reduction, and demonstrated that both cardiac Rol overload and atRA deficiency promote DCM by supplementing T2DM mice with Rol or atRA. Mechanically, by constructing cardiomyocyte-specific conditional RDH10-knockout mice and overexpressing RDH10 in T2DM mice via adeno-associated virus, we verified that the reduction in cardiac retinol dehydrogenase 10 (RDH10) is the initiating factor for cardiac retinol metabolism disorder and its resulting DCM. Additionally, lipotoxicity and ferroptosis contribute to the effect of retinol metabolism disorder on DCM. Based on these results, we suggest that the reduction of cardiac RDH10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying DCM.

GEO Accession ID: GSE202418

PMID: 36864033

Description

Submission Date: May 06, 2022

Summary: Diabetic cardiomyopathy (DCM) is a primary myocardial injury induced by diabetes mellitus (DM) with a complex pathogenesis. In this study, we identified disordered cardiac retinol metabolism in T2DM mice and patients characterized by retinol (vitamin A, Rol) overload, all-trans retinoic acid (atRA) deficiency and retinoic acid receptors (RARs) reduction, and demonstrated that both cardiac Rol overload and atRA deficiency promote DCM by supplementing T2DM mice with Rol or atRA. Mechanically, by constructing cardiomyocyte-specific conditional RDH10-knockout mice and overexpressing RDH10 in T2DM mice via adeno-associated virus, we verified that the reduction in cardiac retinol dehydrogenase 10 (RDH10) is the initiating factor for cardiac retinol metabolism disorder and its resulting DCM. Additionally, lipotoxicity and ferroptosis contribute to the effect of retinol metabolism disorder on DCM. Based on these results, we suggest that the reduction of cardiac RDH10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying DCM.

GEO Accession ID: GSE202418

PMID: 36864033

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