PPAR-γ as a therapeutic target in cardiovascular disease: evidence and uncertainty

Huang, Janice; Greyson, Clifford R.; Schwartz, Gregory G.

doi:10.1194/jlr.r024505

Cited by 61 publications

(49 citation statements)

References 220 publications

(211 reference statements)

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“…The rs1801282 locus is located at exon 2, while rs3856806 is located at exon 6 of the PPARγ gene. PPARγ is associated with nearly all components of MS, including diabetes and obesity (Kota et al, 2005), hyperlipidemia (Wahli and Michalik, 2012), atherosclerosis (Huang et al, 2012), and hypertension.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the PPARγ gene and their association with metabolic syndrome in Uyghurs and Kazakhs from Xinjiang, China

Chen

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We investigated the association between polymorphisms rs1801282 and rs3856806 of the PPARγ gene and metabolic syndrome (MS) among Uyghurs and Kazakhs. Mass spectrometry techniques were used to detect the PPARγ genotypes rs1801282 and rs3856806 in 987 subjects, CC genotype and C allele frequencies were 83.6 and 91.7%, respectively, at rs1801282 in Kazakhs, which were higher than those in Uyghurs (72.3 and 85.0%, respectively; P < 0.05). CC genotype and C allele frequencies were 73.6 and 85.3%, respectively, at the rs3856806 loci in Kazakhs, which were higher than those in Uyghurs (60.7 and 77.9%, respectively; P < 0.05). For the rs3856806 polymorphism in Kazakhs, CT/TT genotype and T allele frequencies were 21.2 and 12.4% for MS subjects, which were lower than those for the control group (31.6 and 17.0%, respectively; P < 0.05). Risk analysis of Kazakhs revealed that individuals with the CT and TT genotypes at rs3856806 had an increased risk, 0.524-and 0.770-fold, respectively, of developing MS than those possessing the CC genotype. Individuals with the T allele also had an increase in risk, by 0.699-fold, of developing MS than those with the C allele. For Uyghurs, those with the CC genotype at rs1801282 had higher systolic blood pressure than those with the CG/GG genotype. Among Kazakhs, those with the CC genotype at rs3856806 had higher triglyceride and waist-hip ratio levels but lower high-density lipoprotein cholesterol levels than those with the CT/TT genotype. The rs1801282 and rs3856806 PPARγ polymorphisms differ between Uyghurs and Kazakhs from Xinjiang Province, China.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms in the PPARγ gene and their association with metabolic syndrome in Uyghurs and Kazakhs from Xinjiang, China

Chen

et al. 2015

Genet. Mol. Res.

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“…The expression and activity of the PPAR-γ and their coactivator protein such as PGC-1α is dynamically regulated in several cardiomyopathic and metabolic diseases. (19)(20)(21) Discovery of PPARs as an important regulator of metabolic pathways has brought us a significant insight of the mechanisms which regulates these processes. PPARs act as nutritional sensors that regulate a variety of homeostatic functions including metabolism, inflammation and development.…”

Section: Ppar-γ Signalingmentioning

confidence: 99%

“…PPARs act as nutritional sensors that regulate a variety of homeostatic functions including metabolism, inflammation and development. (19)(20)(21)(22) PPAR-α is the main metabolic regulator for catabolism whereas PPAR-γ regulates anabolism or storage. PPAR is expressed in cardiovascular system as endothelial cells, vascular smooth muscle cells and monocytes/macrophages.…”

Section: Ppar-γ Signalingmentioning

confidence: 99%

“…(21) PPAR-γ agonists have been shown to block the proliferation and increase the apoptosis of vascular smooth muscle cells, suggesting more beneficial of PPAR-γ activation in vasculature. (19,21) The beneficial effects are largely attributable to anti-inflammation activity of PPAR-γ and its role in modulating lipid homeostasis in macrophages. Vascular inflammation has been increasingly acknowledged as an important factor in the pathogenesis of atherosclerosis.…”

Section: Ppar-γ Signalingmentioning

confidence: 99%

“…(25) The importance of macrophage PPAR-γ in CVD has begun to be appreciated ever since foam cells in atherosclerotic lesions were found to have a high level of PPAR-γ expression. (19)(20)(21)23).…”

Section: Ppar-γ Signalingmentioning

confidence: 99%

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PPAR-gamma Signaling in Metabolic Homeostasis

et al. 2016

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BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-γ, or also known as nuclear receptor subfamily 1 group C member 3 (NR1C3), is a PPAR which serves as master regulator of adipocytes differentiation, and plays an important role in lipid metabolism or adipogenesis. Recent study showed that PPAR-γ is expressed in most tissue and also has critical impact in many metabolic homeostasis disorders.CONTENT: Dysregulation of PPAR-γ is correlated to the development of obesity, type 2 diabetes, atherosclerosis, cardiovascular disease, acute kidney injury, autoimmune disease, gastrointestinal disease and Alzheimer’s disease. Abundant number of new emerging compounds, with in vitro and in vivo effectiveness as natural and synthetic agonists of PPARs, are investigated, developed and used as the treatment of metabolic disorders of glucose and/or lipid and other diseases.SUMMARY: Based on all studies explanation, targeting PPAR-γ is proven to be a good therapeutic method for reducing negative effect of several metabolic homeostasis disorder. Now, many natural and synthetic agonists of PPARs are used as the treatment of metabolic disorders of glucose and/or lipid or another metabolic homeostasis disorder. Such agonists have different properties and specificities for individual PPARs receptors, different absorption and distribution, and distinctive gene expression profiles, which ultimately lead to different clinical outcomes.KEYWORDS: PPAR-γ, dysregulation, agonist, adipogenesis, metabolic disorder, homeostasis

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Discovery and Development of the Next-Generation HCV NS3 Protease Inhibitor Glecaprevir

Wang

Jiang

et al. 2019

Topics in Medicinal Chemistry

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PPAR-γ as a therapeutic target in cardiovascular disease: evidence and uncertainty

Cited by 61 publications

References 220 publications

Polymorphisms in the PPARγ gene and their association with metabolic syndrome in Uyghurs and Kazakhs from Xinjiang, China

Polymorphisms in the PPARγ gene and their association with metabolic syndrome in Uyghurs and Kazakhs from Xinjiang, China

PPAR-gamma Signaling in Metabolic Homeostasis

Discovery and Development of the Next-Generation HCV NS3 Protease Inhibitor Glecaprevir

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