PLK1 promotes cholesterol efflux and alleviates atherosclerosis by up-regulating ABCA1 and ABCG1 expression via the...

Area of Science:

• Cardiovascular Biology
• Molecular Metabolism
• Cellular Signaling

Background:

• Polo-like kinase 1 (PLK1) is implicated in lipid metabolism and cardiovascular disease.
• The specific role of PLK1 in atherogenesis remains largely undetermined.
• Understanding PLK1's function is crucial for developing novel therapeutic strategies against atherosclerosis.

Purpose of the Study:

• To investigate the impact of PLK1 on macrophage lipid accumulation.
• To elucidate the role of PLK1 in the development of atherosclerosis.
• To explore the underlying molecular mechanisms by which PLK1 influences these processes.

Main Methods:

• Utilized lentivirus-mediated overexpression of PLK1 in THP-1 macrophage-derived foam cells.
• Conducted mechanistic studies involving phosphorylation assays and pathway analysis (AMPK/PPARγ/LXRα).
• Employed atherosclerosis model mice (apoE-deficient) with lentiviral vector delivery of PLK1, followed by lipid profile and lesion area analysis.

Main Results:

• PLK1 expression was significantly reduced in lipid-loaded macrophages and atherosclerosis models.
• PLK1 overexpression promoted cholesterol efflux and inhibited lipid accumulation in foam cells.
• PLK1 activated the AMPK/PPARγ/LXRα pathway, up-regulating ABCA1 and ABCG1 expression, enhancing reverse cholesterol transport, and reducing atherosclerotic lesions.

Conclusions:

• PLK1 plays a protective role in atherosclerosis by inhibiting macrophage lipid accumulation.
• PLK1 facilitates cholesterol efflux via the AMPK/PPARγ/LXRα pathway, promoting ABCA1 and ABCG1 expression.
• PLK1 represents a potential therapeutic target for mitigating atherosclerosis and related cardiovascular diseases.