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Atherosclerosis is a chronic inflammatory disease of the arterial wall with lipid-laden lesions, involving a complex interaction between multiple different cell types and cytokine networks. Inflammatory responses mark all stages of atherogenesis: from lipid accumulation in the intima to plaque formation and eventual rupture. One of the most important regulators of inflammation is the transcription factor nuclear factor-κB (NF-κB), which is activated through the canonical and noncanonical pathways in response to various stimuli. NF-κB has long been regarded as a proatherogenic factor, because it is implicated in multiple pathological processes during atherogenesis, including foam cell formation, vascular inflammation, proliferation of vascular smooth muscle cells, arterial calcification, and plaque progression. In contrast, inhibition of NF-κB signaling has been shown to protect against atherosclerosis. This chapter aims to discuss recent progress on the roles of NF-κB in lipid metabolism and atherosclerosis and also to highlight its potential therapeutic benefits.

Atherosclerosis is a chronic inflammatory disease with deposition of excessive cholesterol in the arterial intima. Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor that can activate or inhibit the expression of many target genes by forming a heterodimer complex with the retinoid X receptor. Activation of PPARα plays an important role in the metabolism of multiple lipids, including high-density lipoprotein, cholesterol, low-density lipoprotein, triglyceride, phospholipid, bile acids, and fatty acids. Increased PPARα activity also mitigates atherosclerosis by blocking macrophage foam cell formation, vascular inflammation, vascular smooth muscle cell proliferation and migration, plaque instability, and thrombogenicity. Clinical use of synthetic PPARα agonist fibrate improved dyslipidemia and attenuated atherosclerosis-related disease risk. This review summarizes PPARα in lipid and lipoprotein metabolism and atherosclerosis, and also highlights its potential therapeutic benefits.