Cardiac Plin5 interacts with SERCA2 and promotes calcium handling and cardiomyocyte contractility

The adult heart develops hypertrophy to reduce ventricular wall stress and maintain cardiac function in response to an increased workload. Although pathological hypertrophy generally progresses to heart failure, physiological hypertrophy may be cardioprotective. Cardiac-specific overexpression of th...

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Bibliographic Details
Published in:Life science alliance 2023-04, Vol.6 (4), p.e202201690
Main Authors: Cinato, Mathieu, Mardani, Ismena, Miljanovic, Azra, Drevinge, Christina, Laudette, Marion, Bollano, Entela, Henricsson, Marcus, Tolö, Johan, Bauza Thorbrügge, Marcos, Levin, Max, Lindbom, Malin, Arif, Muhammad, Pacher, Pal, Andersson, Linda, Olofsson, Charlotta S, Borén, Jan, Levin, Malin C
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
Calcium Signaling
Cardiomegaly - genetics
Heart Failure
Humans
Mice
Myocytes, Cardiac - metabolism
Perilipin-5 - metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism
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Summary:The adult heart develops hypertrophy to reduce ventricular wall stress and maintain cardiac function in response to an increased workload. Although pathological hypertrophy generally progresses to heart failure, physiological hypertrophy may be cardioprotective. Cardiac-specific overexpression of the lipid-droplet protein perilipin 5 (Plin5) promotes cardiac hypertrophy, but it is unclear whether this response is beneficial. We analyzed RNA-sequencing data from human left ventricle and showed that cardiac expression correlates with up-regulation of cardiac contraction-related processes. To investigate how elevated cardiac Plin5 levels affect cardiac contractility, we generated mice with cardiac-specific overexpression of (MHC- mice). These mice displayed increased left ventricular mass and cardiomyocyte size but preserved heart function. Quantitative proteomics identified sarcoplasmic/endoplasmic reticulum Ca ATPase 2 (SERCA2) as a Plin5-interacting protein. In situ proximity ligation assay further confirmed the Plin5/SERCA2 interaction. Live imaging showed increases in intracellular Ca release during contraction, Ca removal during relaxation, and SERCA2 function in MHC- versus WT cardiomyocytes. These results identify a role of Plin5 in improving cardiac contractility through enhanced Ca signaling.
ISSN:2575-1077
2575-1077
DOI:10.26508/lsa.202201690