PPARγ对胆固醇代谢及代谢相关基因的影响
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摘要
动脉粥样硬化(atherosclerosis,AS)是一种严重危害人类健康的常见心血管疾病,也是心脑血管疾病最主要的病变基础之一。其发病机制包括脂质浸润学说、炎症学说、血栓形成学说、平滑肌细胞增殖学说等。目前大家对其发生发展的机制已进行了大量的研究。其脂质浸润学说中细胞内胆固醇代谢紊乱导致细胞内脂质聚集形成的泡沫细胞是AS发生和发展的关键步骤。近年来研究发现,过氧化物酶体增殖物受体(PPARγ)是调节脂质代谢的重要转录调节因子,对脂质代谢相关基因表达有重要调节作用并参与AS发生发展的调控。本文就PPARγ对脂质代谢及相关基因调控的相关作用做一些简要介绍。
Atherosclerosis(AS) is a common cardiovascular disease that seriously harms human health, and it is also one of the most important pathological bases of cardiovascular and cerebrovascular diseases. Its pathogenesis includes lipid infiltration theory,inflammation theory, thrombosis theory, smooth muscle cell proliferation theory and so on. At present, a lot of research has been done on the mechanism of its occurrence and development. In the theory of lipid infiltration, the foam cells formed by aggregation of lipids in the cell caused by cholesterol metabolism disorder are the key steps for the occurrence and development of AS. In recent years, it has been found that peroxisome proliferator receptor(PPARgam) is an important transcriptional regulator regulating lipid metabolism. It plays an important role in regulating gene expression related to lipid metabolism and in regulating the occurrence and development of AS. In this paper, we briefly introduced the role of PPARgamma in lipid metabolism and related gene regulation.
Atherosclerosis(AS) is a common cardiovascular disease that seriously harms human health, and it is also one of the most important pathological bases of cardiovascular and cerebrovascular diseases. Its pathogenesis includes lipid infiltration theory,inflammation theory, thrombosis theory, smooth muscle cell proliferation theory and so on. At present, a lot of research has been done on the mechanism of its occurrence and development. In the theory of lipid infiltration, the foam cells formed by aggregation of lipids in the cell caused by cholesterol metabolism disorder are the key steps for the occurrence and development of AS. In recent years, it has been found that peroxisome proliferator receptor(PPARgam) is an important transcriptional regulator regulating lipid metabolism. It plays an important role in regulating gene expression related to lipid metabolism and in regulating the occurrence and development of AS. In this paper, we briefly introduced the role of PPARgamma in lipid metabolism and related gene regulation.
引文
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[12]LAFFITTE BA,JOSEPH SB,WALCZAK R,et al.Autoregulation of the human liver X receptor alpha promoter[J].Molecular&Cellular Biology2001,21(22):7558-7568.
[13]JIANMEI,Y,BO,L,QINGPING,J,QINGBO,G.Salvianolic acid Baccelerated ABCA1-dependent cholesterol efflux by targeting PPAR-γand LXRα[J].Biochemical and Biophysical Research Communications,2015462(3):233-238.
[14]TOH SA,MILLAR JS,BILLHEIMER J,et al.PPARγactivation redirects macrophage cholesterol from fecal excretion to adipose tissue uptake in mice via SR-BI[J].Biochemical Pharmacology,2011,81(7):934-941.
[15]Nagy L,Tontonoz P,Alvarez JG,et al.Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma[J]Cell,1998,93:229-240.
[16]Date D,Das R,Narla G,et al.Kruppel-like transcription factor 6 regulates inflammatory macrophage polarization[J].J Biol Chem,2014,289(15):10318-10329.
[17]Bechmann LP,Vetter D,Ishida J,et al.Post-transcriptional activation of PPAR alpha by KLF6 in hepatic steatosis[J].J Hepatol,2013,58(5):1000-1006.
[2]NANPING WANG,RUIYING YIN,YAN LIU,et al.Role of Peroxisome Proliferator-Activated Receptor-γin Atherosclerosis[J].Molecular Medicine Reports,2014,75(3):1755-1760.
[3]CHANDRA M,PANCHATCHARAM M,MIRIVALA S.PPARγand Its Role in Cardiovascular Diseases[J].Ppar Research,2017,2017(4-5):6404638.
[4]MONSALVE FA,PYARASANI RD,DELGADO-LOPEZ F,et al.Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases[J].Mediators Inflamm,2013:549627.
[5]梁荣,霍清萍.过氧化物酶体增殖物激活受体γ对动脉粥样硬化的作用及其中医药研究进展[J].中西医结合心脑血管病杂志,201614(17):2019-2021.
[6]STAELS B.PPARgamma and atherosclerosis[J].Current Medical Research&Opinion,2005,21(1):S13.
[7]PARK Y,PHAM TX,LEE J.Lipopolysaccharide represses the expression of ATP-binding cassette transporter G1 and scavenger receptor class B,type I in murine macrophages[J].Inflammation Research,2012,61(5):465-472.
[8]曾颖.过氧化体增殖物激活型受体γ对巨噬细胞脂质蓄积及CD36表达的影响[J].中国动脉硬化杂志,2012,20(2):121-124.
[9]HU Q,ZHANG XJ,LIU CX,et al.PPARgamma-induced caveolin-1enhances cholesterol efflux and attenuates atherosclerosis in apolipoprotein E-deficient mice[J].J Vasc Res,2010,47(1):69-79.
[10]IKHLEF S,BERROUGUI H,KAMTCHUENG S,et al.Paraoxonase1-treated oxLDL promotes cholesterol efflux from macrophages by stimulating the PPARγLXRαABCA1 pathway[J].FEBS Lett,2016,590(11)1614-1629.
[11]OGATA M,TSUJITA MHOSSAIN MA.On the mechanism for PPARagonists to enhance ABCA1 gene expression[J].Atherosclerosis,2009205(2):413-419.
[12]LAFFITTE BA,JOSEPH SB,WALCZAK R,et al.Autoregulation of the human liver X receptor alpha promoter[J].Molecular&Cellular Biology2001,21(22):7558-7568.
[13]JIANMEI,Y,BO,L,QINGPING,J,QINGBO,G.Salvianolic acid Baccelerated ABCA1-dependent cholesterol efflux by targeting PPAR-γand LXRα[J].Biochemical and Biophysical Research Communications,2015462(3):233-238.
[14]TOH SA,MILLAR JS,BILLHEIMER J,et al.PPARγactivation redirects macrophage cholesterol from fecal excretion to adipose tissue uptake in mice via SR-BI[J].Biochemical Pharmacology,2011,81(7):934-941.
[15]Nagy L,Tontonoz P,Alvarez JG,et al.Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma[J]Cell,1998,93:229-240.
[16]Date D,Das R,Narla G,et al.Kruppel-like transcription factor 6 regulates inflammatory macrophage polarization[J].J Biol Chem,2014,289(15):10318-10329.
[17]Bechmann LP,Vetter D,Ishida J,et al.Post-transcriptional activation of PPAR alpha by KLF6 in hepatic steatosis[J].J Hepatol,2013,58(5):1000-1006.