The role of peroxisome proliferator‐activated receptor γ in lipid metabolism and inflammation in atherosclerosis

Abstract

Cardiovascular disease events are the result of functional and structural abnormalities in the arteries and heart. Atherosclerosis is the main cause and pathological basis of cardiovascular diseases. Atherosclerosis is a multifactorial disease associated with dyslipidemia, inflammation, and oxidative stress, among which dyslipidemia and chronic inflammation occur in all processes. Under the influence of lipoproteins, the arterial intima causes inflammation, necrosis, fibrosis, and calcification, leading to plaque formation in specific parts of the artery, which further develops into plaque rupture and secondary thrombosis. Foam cell formation from macrophages is an early event in the development of atherosclerosis. Lipid uptake causes a vascular inflammatory response, and persistent inflammatory infiltration in the lesion area further promotes the development of the disease. Inhibition of macrophage differentiation into foam cell and reduction of the level of proinflammatory factors in macrophages can effectively alleviate the occurrence and development of atherosclerosis. Peroxisome proliferator-activated receptor γ (PPARγ) is a ligandactivated nuclear receptor that plays an important antiatherosclerotic role by regulating triglyceride metabolism, lipid uptake, cholesterol efflux, macrophage polarity, and inhibiting inflammatory signaling pathways. In addition, PPARγ shifts its binding to ligands and co-activators or co-repressors of transcription of target genes through posttranslational modification, thereby affecting the regulation of its downstream target genes. Many ligand agonists have also been developed targeting PPARγ. In this review, we summarized the role of PPARγ in lipid metabolism and inflammation in development of atherosclerosis, the posttranslational regulatory mechanism of PPARγ, and further discusses the value of PPARγ as an antiatherosclerosis target.

Etrinabdione (VCE-004.8), a B55α activator, promotes angiogenesis and arteriogenesis in critical limb ischemia

“…In addition, VCE-004.8 is a dual agonist of PPARγ and CB2R 14 . PPARg and CB2R are preclinically validated therapeutic targets for vascular inflammation and atherosclerosis 45,46,47 . For instance, foam cells play a vital role in the initiation and development of atherosclerosis since they are the major sources of necrotic core in atherosclerotic plaques.…”

Efficacy and potential mechanism of atherosclerosis prevention by the active components of leech based on network pharmacology combined with animal experiments

“…PPARG is involved in multitarget and multipathway anti-AS actions such as inflammatory response, myocardial vascular smooth muscle value-added, and vascular endothelial function. The expression of TNF-α, IL-1β, and IL-6 in rat aorta was significantly increased after intervention with PPARG inhibitor in a high-fat-diet-induced rat model, indicating that PPARG has a clear anti-inflammatory effect [ [41] , [42] , [43] ]. SRC is involved in the progression of AS by promoting cell proliferation, migration, and lipid accumulation.…”

Single-nucleus RNA-sequencing reveals NRF1/NFE2L1 as a key factor determining the thermogenesis and cellular heterogeneity and dynamics of brown adipose tissues in mice

“…In the current study, although we have provided no evidence that the key lipolytic genes are direct downstream transcriptional targets of NFE2L1, RNA profiles of BAC/BAT of current study along with previous findings on the mRNA expression of lipolytic genes in WAC/WAT [ 11 , [18] , [19] , [20] , [21] ] highly suggest that NFE2L1 is one of the key factors that control the transcription of the lipolytic genes. In addition, emerging evidence indicates that multiple factors, PPARγ in particular, are involved in the transcriptional activation or repression of the key lipolytic genes [ 40 , 41 ]. Interestingly, our previous mechanistic studies in 3T3-L1 cells indicated that NFE2L1 regulates the expression of Pparγ2 in an isoform-specific manner [ 21 ].…”