Electroacupuncture improves cardiac function in hyperlipidemic rats by enhancing efferocytosis in myocardial macrophages via the PPARγ-LXRα-MerTK pathway

Background and aim

Electroacupuncture (EA) is an effective treatment for hyperlipidemia because it decreases the protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor alpha (LXRα). Lowering blood lipids can reverse cardiac insufficiency, but the underlying mechanisms remain unclear. We aimed to explore whether EA reduces blood lipid levels and restores cardiac function in hyperlipidemic rats and to elucidate the underlying mechanism involved.

Procedures

A hyperlipidemic rat model was established by providing the animals with a high-fat diet (HFD). Animals were divided into normal control diet (NC), HFD, PPARγ siRNA, EA, and EA + PPARγ siRNA groups. H&E staining was used to observe the histopathology of the heart and liver. Transmission electron microscopy and oil red O staining were used to detect the distribution of myocardial lipid droplets and the efferocytosis of macrophages. Double immunofluorescence was used to detect the expression of ATP binding cassette transport A1 (ABCA1), ATP binding cassette transport G1 (ABCG1), PPARγ, LXR, and MER proto-oncogene tyrosine kinase (MerTK) in cardiac macrophages. The MerTK−/− rats and littermate wild-type rats were divided into NC, HFD, and EA groups. The efferocytosis rate of myocardial macrophages in different groups was detected using TUNEL and Annexin V-FITC/PI double staining.

Results and conclusion

EA had positive effects on the blood lipid profile, cardiac function, and heart and liver weights; reduced fat deposition in cardiomyocytes and hepatocytes; promoted reverse cholesterol transport; and enhanced macrophage efferocytosis in HFD-fed rats. This effect was blocked by PPARγ siRNA. The protein expression of the PPARγ-LXRα-MerTK pathway was also increased by EA treatment. However, under MerTK−/− conditions, the beneficial effects of EA on efferocytosis in myocardial macrophages were blocked. EA reversed ectopic lipid deposition in the liver and heart, increased efferocytosis in myocardial macrophages, improved hyperlipidemia, and ameliorated cardiac dysfunction in HFD-fed rats through the PPARγ-LXRα-MerTK pathway.