Cardiac Plin5 interacts with SERCA2 and promotes calcium handling and cardiomyocyte contractility.
Mathieu CinatoIsmena MardaniAzra MiljanovicChristina DrevingeMarion LaudetteEntela BollanoMarcus StahlmanJohan TolöMarcos Bauza ThorbrüggeMax LevinMalin LindbomMuhammad ArifPal PacherLinda AnderssonCharlotta S OlofssonJan BorénMalin C LevinPublished in: Life science alliance (2023)
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 Ca 2+ 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 2+ release during contraction, Ca 2+ 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 Ca 2+ signaling.
Keyphrases
- left ventricular
- heart failure
- mitral valve
- cardiac resynchronization therapy
- endoplasmic reticulum
- hypertrophic cardiomyopathy
- high resolution
- acute myocardial infarction
- cell proliferation
- smooth muscle
- atrial fibrillation
- left atrial
- metabolic syndrome
- protein kinase
- poor prognosis
- pulmonary hypertension
- small molecule
- coronary artery
- machine learning
- aortic stenosis
- young adults
- type diabetes
- big data
- coronary artery disease
- stress induced
- drug induced
- fluorescence imaging