Cav-1 deficiency induces cardiac dysfunction via the AdipoR1-AMPK-mTOR autophagy pathway

This study aimed to investigate the mechanism by which Caveolin-1 (Cav-1) deficiency leads to cardiac dysfunction, utilizing both in vivo and in vitro experimental models.

Experiments used 43-52-week-old wild-type (WT) and Cav-1 knockout (Cav-1^-/-) mice (n=5 per group), and the H9C2 rat cardiomyocyte cell line.

In vivo, Cav-1^-/-mice received rapamycin (0.25 mg/kg). In vitro, H9C2 cells underwent Cav-1 knockdown/overexpression and were treated with rapamycin (100 nM), chloroquine (20 µM), AMPK activator A-769662, adiponectin (APN, 5 µg/ml), or AdipoR1 overexpression.

Cardiac function was assessed by echocardiography (LVEF, LVFS). Protein expression was analyzed via western blotting and immunofluorescence. Autophagic flux was measured using mRFP-GFP-LC3B lentivirus. Apoptosis was evaluated by TUNEL staining and flow cytometry. Data are mean ± SD; statistical analysis used t-tests/ANOVA.

Cav-1^-/- mice exhibited impaired cardiac function (LVEF: reduced vs. WT, p<0.05), suppressed autophagy, increased apoptosis, and elevated inflammation/fibrosis. In H9C2 cells, Cav-1 knockdown inhibited AMPK phosphorylation, activated mTOR, and repressed autophagy, effects reversed by Cav-1 overexpression or rapamycin/AMPK activation. Bioinformatic and immunofluorescence analyses identified AdipoR1 downregulation in Cav-1^-/- hearts; APN/AdipoR1 overexpression rescued autophagy and reduced apoptosis.

Cav-1 deficiency induces cardiac dysfunction by suppressing autophagy via the AdipoR1-AMPK-mTOR pathway, highlighting Cav-1 as a potential therapeutic target for cardiac dysfunction.