SWAP70 Promotes Atherosclerosis Via Endothelial CAV1 Nuclear Translocation.

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Endothelial Cell Biology

Background:

• Atherosclerosis, a primary cause of coronary artery disease, stems from disturbed blood flow and chronic endothelial inflammation.
• Switch-associated protein 70 (SWAP70) is genetically linked to coronary artery disease but its role in atherogenesis is unclear.

Purpose of the Study:

• To investigate the functional role of SWAP70 in vascular inflammation and atherosclerotic plaque development.
• To elucidate the molecular mechanisms by which SWAP70 influences endothelial responses to mechanical stress and inflammation.

Main Methods:

• Utilized endothelial cell-specific Swap70 overexpression and knockout mouse models.
• Employed lentiviral overexpression and siRNA knockdown in human umbilical vein endothelial cells.
• Conducted in vitro assays under oscillatory shear stress and cytokine stimulation, alongside mechanistic studies including co-immunoprecipitation and RNA sequencing.

Main Results:

• SWAP70 expression increased under oscillatory shear stress and in human atherosclerotic plaques.
• SWAP70 facilitated caveolin-1 nuclear translocation, enhancing inflammatory gene expression.
• Endothelial-specific Swap70 deletion attenuated atherosclerosis in vivo, while overexpression exacerbated inflammation.

Conclusions:

• SWAP70 acts as a mechano-responsive regulator of endothelial inflammation and atherosclerosis via a novel SWAP70-CAV1 signaling axis.
• Targeting the SWAP70-CAV1 interaction presents a potential therapeutic strategy for atherosclerotic cardiovascular disease.