FIGURE 1.

The role of protein kinase C isoforms in the initiation and progression of atherosclerosis. The pathophysiology of atherosclerosis begins with the retention of circulating low-density lipoproteins (LDL) in the intima. Excess levels of circulating LDL are cleared via hepatic LDL receptor, which is regulated by protein kinase Cα (PKCα) and PKCβ. The intimal LDLs are prone to oxidative modification by environmental oxidizing enzymes to become oxidized LDLs (oxLDLs), which activate endothelial cells (ECs) to express adhesion molecules. The major PKC isoforms involved in this step are PKCα and PKCβ. PKCα, PKCδ, and PKCζ regulate the expression of ATP-binding cassette transporter A1, which plays a key role in macrophage cholesterol efflux. PKCβ and PKCδ regulate foam cell formation via manipulating scavenger receptor-mediated uptake of oxLDLs by macrophages. Vascular smooth muscle cells (VSMCs) proliferate and migrate from the media to the intima in response to environmental stimuli. PKCδ plays a critical role in regulating VSMC function during atherosclerosis. Both innate and adaptive immune systems are involved in the atherosclerotic process. Apoptosis of VSMCs and secretion of matrix metalloproteinases (MMPs) from macrophages are critical for plaque complexity. PKCδ is the principal isoform regulating VSMC apoptosis. Finally, PKCβII had been proposed to regulate MMP secretion in ECs during atherosclerosis.