RT Journal Article
SR Electronic
T1 Cardiac Plin5 interacts with SERCA2 and promotes calcium handling and cardiomyocyte contractility
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201690
DO 10.26508/lsa.202201690
VO 6
IS 4
A1 Cinato, Mathieu
A1 Mardani, Ismena
A1 Miljanovic, Azra
A1 Drevinge, Christina
A1 Laudette, Marion
A1 Bollano, Entela
A1 Henricsson, Marcus
A1 Tolö, Johan
A1 Bauza Thorbrügge, Marcos
A1 Levin, Max
A1 Lindbom, Malin
A1 Arif, Muhammad
A1 Pacher, Pal
A1 Andersson, Linda
A1 Olofsson, Charlotta S
A1 Borén, Jan
A1 Levin, Malin C
YR 2023
UL https://www.life-science-alliance.org/content/6/4/e202201690.abstract
AB 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 PLIN5 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 Plin5 (MHC-Plin5 mice). These mice displayed increased left ventricular mass and cardiomyocyte size but preserved heart function. Quantitative proteomics identified sarcoplasmic/endoplasmic reticulum Ca2+ 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 Ca2+ release during contraction, Ca2+ removal during relaxation, and SERCA2 function in MHC-Plin5 versus WT cardiomyocytes. These results identify a role of Plin5 in improving cardiac contractility through enhanced Ca2+ signaling.