Abstract
Foam cells are specialized lipid-loaded macrophages derived from monocytes and are a key pathological feature of atherosclerotic lesions. Lysophosphatidylcholine (LPC) is a major lipid component of the plasma membrane with a broad spectrum of proinflammatory activities and plays a key role in atherosclerosis. However, the role of LPC in lipid droplet (LD) biogenesis and the modulation of inflammasome activation is still poorly understood. In the present study, we investigated whether LPC can induce foam cell formation through an analysis of LD biogenesis and determined whether the cell signaling involved in this process is mediated by the inflammasome activation pathway in human endothelial cells and monocytes. Our results showed that LPC induced foam cell formation in both types of cells by increasing LD biogenesis via a NLRP3 inflammasome-dependent pathway. Furthermore, LPC induced pyroptosis in both cells and the activation of the inflammasome with IL-1β secretion, which was dependent on potassium efflux and lysosomal damage in human monocytes. The present study described the IL-1β secretion and foam cell formation triggered by LPC via an inflammasome-mediated pathway in human monocytes and endothelial cells. Our results will help improve our understanding of the relationships among LPC, LD biogenesis, and NLRP3 inflammasome activation in the pathogenesis of atherosclerosis.
Highlights
Atherosclerosis is caused by a proinflammatory process [1] mediated by the deposition of excess lipids in the arterial intima [2], resulting in the development of lesions in the arterial walls
We investigated the mechanisms related to lipid metabolism involved in LPCinduced lipid droplet (LD) biogenesis
Our results showed that inhibition of PPARγ decreases LD biogenesis in human monocytes stimulated with LPC (Figure 1D)
Summary
Atherosclerosis is caused by a proinflammatory process [1] mediated by the deposition of excess lipids in the arterial intima [2], resulting in the development of lesions in the arterial walls. These atherosclerotic lesions are fibro-fatty plaques in the intima of arteries [3] characterized by abundant cells with multiple lipid droplets (LDs) in the cytoplasm. The major bioactive lipid component of oxLDL is the phospholipid lysophosphatidylcholine (LPC) [4, 8, 9] This lipid is thought to be responsible for many of the inflammatory effects of oxLDL and is reported to increase atherosclerotic lesions [9,10,11]
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