低剪切应力与动脉粥样硬化形成研究新进展
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摘要
动脉粥样硬化病变为动脉内膜损伤诱导性增生,好发于动脉的分叉和分支等低剪切应力(LSS)区域。LSS通过激活细胞上的膜感受器和细胞内信号转导而调节基因表达以及表型的转变,在动脉粥样硬化病变的发生和发展中起着重要作用。本文综述了LSS与内皮细胞炎症、内皮间质转化、内皮细胞自噬间的关系及其调控机制,期望为动脉粥样硬化防治提供新的思路和策略。
The process of atherosclerotic lesions is a proliferative response induced by arterial intimal injury, which occurs in the bifurcation and branching regions of the arteries with low shear stress(LSS). LSS regulates gene expression and phenotype transformation by activating membrane receptors and intracellular signal transduction on cells, and plays an important role in the occurrence and development of atherosclerosis. This article reviews the relationship between LSS and endothelial cell inflammation, endothelial-to-mesenchymal transition, endothelial cell autophagy and its regulatory mechanism, hoping to provide new ideas and strategies for the prevention and treatment of atherosclerosis.
The process of atherosclerotic lesions is a proliferative response induced by arterial intimal injury, which occurs in the bifurcation and branching regions of the arteries with low shear stress(LSS). LSS regulates gene expression and phenotype transformation by activating membrane receptors and intracellular signal transduction on cells, and plays an important role in the occurrence and development of atherosclerosis. This article reviews the relationship between LSS and endothelial cell inflammation, endothelial-to-mesenchymal transition, endothelial cell autophagy and its regulatory mechanism, hoping to provide new ideas and strategies for the prevention and treatment of atherosclerosis.
引文
[1]Li Y,Lui KO.Reassessing endothelial-to-mesenchymal transition in cardiovascular diseases[J].Nat Rev Cardiol,2018,15(8):445-456.
[2]Li X,Yang Q,Wang Z,et al.Shear stress in atherosclerotic plaque determination[J].DNA Cell Biol,2014,33(12):830-838.
[3]Koskinas KC,Sukhova GK,Baker AB,et al.Thin-capped atheromata with reduced collagen contentin pigs develop in coronary arterial regions exposed to persistently low endothelial shear stress[J].Arterioscler Thromb Vasc Biol,2013,33(7):1494-504.
[4]Papafaklis MI,Takahashi S,Antoniadis AP,et al.Effect of the local hemodynamic environment on the de novo development and progression of eccentric coronary atherosclerosis in humans:insights from prediction[J].Atherosclerosis,2015,240(1):205-11.
[5]Stone PH,Maehara A,Coskun AU,et al.Role of low endothelial shear stress and plaque characteristics in the prediction of nonculprit major adverse cardiac events:the prospect study[J].JACC Cardiovasc Imaging,2018,11(3):462-471.
[6]Hua Q,Tan J,Liu DX,et al.The changes and impact factors of carotid-femoral and carotid-radial pulse wave velocity in patients with essential hypertension[J].Zhonghua Xin Xue Guan Bing Za Zhi,2005,33(12):1088-1091.
[7]Chao Y,Zhu L,Qu X,et al.Inhibition of angiotension II type 1 receptor reduced human endothelial inflammation induced by low shear stress[J].Exp Cell Res,2017,360(2):94-104.
[8]Zhang X,Feng X,Cai W,et al.Chemokine CX3CL1 and its receptor CX3CR1 are associated with human atherosclerotic lesion volnerability[J].Thromb Res,2015,135(6):1147-1153.
[9]Babendreyer A,Molls L,Dreymueller D,et al.Shear stress counteracts endothelial CX3CL1 induction and monocytic cell adhesion[J].Mediators Inflamm,2017,2017:1515389.
[10]Aoki T,Yamamoto K,Fukuda M,et al.Sustained expression of MCP-1 by low wall shear stress loading concomitant with turbulent flow on endothelial cells of intracranial aneurysm[J].Acta Neuropathol Commun,2016,4(1):48.
[11]Ding Z,Liu S,Wang X,et al.Hemodynamic shear stress via ROSmodulates PCSK9 expression in human vascular endothelial and smooth muscle cells and along the mouse aorta[J].Antioxid Redox Signal,2015,22(9):760-771.
[12]Mallavia B,Recio C,Oguiza A,et al.Peptide inhibitor of NF-κBtranslocation ameliorates experimental atherosclerosis[J].Am JPathol,2013,182(5):1910-1921.
[13]Zakkar M,Angelini GD.Regulation of vascular endothelium inflammatory signalling by shear stress[J].Curr Vasc Pharmacol,2016,14(2):181-186.
[14]Wesseling M,Sakkers TR,de Jager SCA,et al.The morphological and molecular mechanisms of epithelial/endothelial-tomesenchymal transition and its involvement in atherosclerosis[J].Vascul Pharmacol,2018,106:1-8.
[15]Hu Y,Guo X,Wang J,et al.A novel microRNA identified in hepatocellular carcinomas is responsive to LEF1 and facilitates proliferation and epithelial-mesenchymal transition via targeting of NFIX[J].Oncogenesis,2018,7(2):22.
[16]Arraf AA,Yelin R,Reshef I,et al.Establishment of the visceral embryonic midline is a dynamic process that requires bilaterally symmetric BMP signaling[J].Dev Cell,2016,37(6):571-580.
[17]Chen PY,Qin L,Baeyens N,et al.Endothelial-to-mesenchymal transition drives atherosclerosis progression[J].J Clin Invest,2015,125(12):4514-4528.
[18]Moonen JR,Lee ES,Schmidt M,et al.Endothelial-tomesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress[J].Cardiovasc Res,2015,108(3):377-386.
[19]Mahmoud MM,Kim HR,Xing R,et al.TWIST1 integrates endothelial responses to flow in vascular dysfunction and atherosclerosis[J].Circ Res,2016,119(3):450-462.
[20]Criem N,Zwijsen A.The epicardium obscures interpretations on endothelial-to-mesenchymal transition in the mouse atrioventricular canal explant assay[J].Sci Rep,2018,8(1):4722.
[21]Cai Z,Shen L,He B,et al.Moving with and beyond cantos:how to put out the fire of inflammation in atherosclerosis[J].Int J Cardiol,2015,195:45-47.
[22]Wu M,Peng Z,Zu C,et al.Losartan attenuates myocardial endothelial-to-mesenchymal transition in spontaneous hypertensive rats via inhibiting TGF-β/Smad signaling[J].PLoS One,2016,11(5):e0155730.
[23]Koga M,Yamauchi A,Kanaoka Y,et al.BMP4 is increased in the aortas of diabetic Apo E knockout mice and enhances uptake of oxidized low density lipoprotein into peritoneal macrophages[J].Inflamm,2013,10(1):32.
[24]Lopez D,Niu G,Huber P,et al.Tumorinduced upregulation of Twist,Snail,and Slug represses the bactivity of the human VE-cadherin promoter[J].Arch Biochem Biophys,2009,482(1-2):77-82.
[25]Mahmoud MM,Serbanovic-Canic J,Feng S,et al.Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail[J].Sci Rep,2017,7(1):3375.
[26]Mahler GJ,Farrar EJ.Inflammatory cytokines promote mesenchymal transformation in embryonic and adult valve endothelial cells[J].Arterioscler Thromb Vasc Biol,2013,33(1):121-130.
[27]Sheng X,Liu Y,Wang J,et al.HUVECs respond to low shear stress stimulation by activating Wnt/β-catenin signaling pathway[J].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi,2017,33(12):1657-1661.
[28]Lee WJ,Park JH,Shin JU,et al.Endothelial-to-mesenchymal transition induced by Wnt 3a in keloid pathogenesis[J].Wound Repair Regen,2015,23(3):435-442.
[29]Evrard SM,Lecce L,Michelis KC,et al.Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability[J].Nat Commun,2016,7:e11853.
[30]Hill JA,Olson EN.Cardiac plasticity[J].N Engl J Med,2008,358(13):1370-1380.
[31]Correia AC,Moonen JR,Brinker MG,et al.FGF2 inhibits endothelial-mesenchymal transition through microRNA-20a-mediated repression of canonical TGF-βsignaling[J].J Cell Sci,2016,129(3):569-579.
[32]Katsura A,Suzuki HI,Ueno T,et al.MicroRNA-31 is a positive modulator of endothelial-mesenchymal transition and associated secretory phenotype induced by TGF-β[J].Genes Cells,2016,21(1):99-116.
[33]Harvald EB,Olsen AS,Frgeman NJ,et al.Autophagy in the light of sphingolipid metabolism[J].Apoptosis,2015,20(5):658-670.
[34]Grimmel M,Backhaus C,Proikas-Cezanne T,et al.WIPI-mediated autophagy and longevity[J].Cells,2015,4(2):202-217.
[35]Guo FX,Hu YW,Zheng L,et al.Shear stress in autophagy and its possible mechanisms in the process of atherosclerosis[J].DNACell Biol,2017,36(5):335-346.
[36]Lien SC,Chang SF,Lee PL,et al.Mechanical regulation of cancer cell apoptosis and autophagy:roles of bone morphogenetic protein receptor,Smad1/5,and p38MAPK[J].Biochim Biophys Acta,2013,1833(12):3124-3133.
[37]Kim J,Kundu M,Viollet B,et al.AMPK and m TOR regulate autophagy through direct phosphorylation of Ulk1[J].Nat Cell Biol,2011,13(2):132-141.
[38]Yang Q,Li X,Li R,et al.Low shear stress inhibited endothelial cell autophagy through TET2 downregulation[J].Ann Biomed Eng,2016,44(7):2218-2227.
[39]Han J,Pan XY,Xu Y,et al.Curcumin induces autophagy to protect vascular endothelial cell survival from oxidative stress damage[J].Autophagy,2012,8(5):812-825.
[40]Chen ML,Yi L,Jin X,et al.Resveratrol attenuates vascular endothelial inflammation by inducing autophagy through the c AMPsignaling pathway[J].Autophagy,2013,9(12):2033-2045.
[41]Uberti F,Lattuada D,Morsanuto V,et al.Vitamin D protects human endothelial cells from oxidative stress through the autophagic and survival pathways[J].J Clin Endocrinol Metab,2014,99(4):1367-1374.
[42]Muller C,Salvayre R,Negre-Salvayre A,et al.Oxidized LDLs trigger endoplasmic reticulum stress and autophagy:prevention by HDLs[J].Autophagy,2011,7(5):541-543.
[43]Torisu T,Torisu K,Lee IH,et al.Autophagy regulates endothelial cell processing,maturation and secretion of von Willebrand factor[J].Nat Med,2013,19(10):1281-1287.
[44]Medici D,Kalluri R.Endothelial-mesenchymal transition and its contribution to the emergence of stem cell phenotype[J].Semin Cancer Biol,2012,22(5-6):379-384.
[45]Menghini R,Casagrande V,Marino A,et al.MiR-216a:a link between endothelial dysfunction and autophagy[J].Cell Death Dis,2014,5:e1029.
[46]Sun L,Zhao M,Liu A,et al.Shear stress induces phenotypic modulation of vascular smooth muscle cells via AMPK/m TOR/ULK1-mediated autophagy[J].Cell Mol Neurobiol,2018,38(2):541-548.
[47]Wang L,Han Y,Shen Y,et al.Endothelial insulin-like growth factor-1 modulates proliferation and phenotype of smooth muscle cells induced by low shear stress[J].Ann Biomed Eng,2014,42(4):776-786.
[48]Levine B,Yuan J.Autophagy in cell death:an innocent convict[J].J Clin Inves,2005,115(10):2679-2688.
[49]Moore KJ,Koplev S,Fisher EA,et al.Macrophage trafficking,inflammatory resolution,and genomics in atherosclerosis:JACC macrophage in CVD series[J].J Am Coll Cardiol,2018,72(18):2181-2197.
[50]uimet M,Franklin V,Mak E,et al.Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase[J].Cell Metab,2011,13(6):655-667.
[51]Finn AV,Nakano M,Narula J,et al.Concept of vulnerable/unstable plaque[J].Arterioscler Thromb Vasc Biol,2010,30(7):1282-1292.
[52]Martinet W,De Meyer I,Verheye S,et al.Drug-induced macrophage autophagy in atherosclerosis:for better or worse[J].Basic Res Cardiol,2013,108(1):321.
[53]Martinet W,De Loof H,De Meyer GR,et al.m TOR inhibition:a promising strategy for stabilization of atherosclerotic plaques[J].Atherosclerosis,2014,233(2):601-607.
[2]Li X,Yang Q,Wang Z,et al.Shear stress in atherosclerotic plaque determination[J].DNA Cell Biol,2014,33(12):830-838.
[3]Koskinas KC,Sukhova GK,Baker AB,et al.Thin-capped atheromata with reduced collagen contentin pigs develop in coronary arterial regions exposed to persistently low endothelial shear stress[J].Arterioscler Thromb Vasc Biol,2013,33(7):1494-504.
[4]Papafaklis MI,Takahashi S,Antoniadis AP,et al.Effect of the local hemodynamic environment on the de novo development and progression of eccentric coronary atherosclerosis in humans:insights from prediction[J].Atherosclerosis,2015,240(1):205-11.
[5]Stone PH,Maehara A,Coskun AU,et al.Role of low endothelial shear stress and plaque characteristics in the prediction of nonculprit major adverse cardiac events:the prospect study[J].JACC Cardiovasc Imaging,2018,11(3):462-471.
[6]Hua Q,Tan J,Liu DX,et al.The changes and impact factors of carotid-femoral and carotid-radial pulse wave velocity in patients with essential hypertension[J].Zhonghua Xin Xue Guan Bing Za Zhi,2005,33(12):1088-1091.
[7]Chao Y,Zhu L,Qu X,et al.Inhibition of angiotension II type 1 receptor reduced human endothelial inflammation induced by low shear stress[J].Exp Cell Res,2017,360(2):94-104.
[8]Zhang X,Feng X,Cai W,et al.Chemokine CX3CL1 and its receptor CX3CR1 are associated with human atherosclerotic lesion volnerability[J].Thromb Res,2015,135(6):1147-1153.
[9]Babendreyer A,Molls L,Dreymueller D,et al.Shear stress counteracts endothelial CX3CL1 induction and monocytic cell adhesion[J].Mediators Inflamm,2017,2017:1515389.
[10]Aoki T,Yamamoto K,Fukuda M,et al.Sustained expression of MCP-1 by low wall shear stress loading concomitant with turbulent flow on endothelial cells of intracranial aneurysm[J].Acta Neuropathol Commun,2016,4(1):48.
[11]Ding Z,Liu S,Wang X,et al.Hemodynamic shear stress via ROSmodulates PCSK9 expression in human vascular endothelial and smooth muscle cells and along the mouse aorta[J].Antioxid Redox Signal,2015,22(9):760-771.
[12]Mallavia B,Recio C,Oguiza A,et al.Peptide inhibitor of NF-κBtranslocation ameliorates experimental atherosclerosis[J].Am JPathol,2013,182(5):1910-1921.
[13]Zakkar M,Angelini GD.Regulation of vascular endothelium inflammatory signalling by shear stress[J].Curr Vasc Pharmacol,2016,14(2):181-186.
[14]Wesseling M,Sakkers TR,de Jager SCA,et al.The morphological and molecular mechanisms of epithelial/endothelial-tomesenchymal transition and its involvement in atherosclerosis[J].Vascul Pharmacol,2018,106:1-8.
[15]Hu Y,Guo X,Wang J,et al.A novel microRNA identified in hepatocellular carcinomas is responsive to LEF1 and facilitates proliferation and epithelial-mesenchymal transition via targeting of NFIX[J].Oncogenesis,2018,7(2):22.
[16]Arraf AA,Yelin R,Reshef I,et al.Establishment of the visceral embryonic midline is a dynamic process that requires bilaterally symmetric BMP signaling[J].Dev Cell,2016,37(6):571-580.
[17]Chen PY,Qin L,Baeyens N,et al.Endothelial-to-mesenchymal transition drives atherosclerosis progression[J].J Clin Invest,2015,125(12):4514-4528.
[18]Moonen JR,Lee ES,Schmidt M,et al.Endothelial-tomesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress[J].Cardiovasc Res,2015,108(3):377-386.
[19]Mahmoud MM,Kim HR,Xing R,et al.TWIST1 integrates endothelial responses to flow in vascular dysfunction and atherosclerosis[J].Circ Res,2016,119(3):450-462.
[20]Criem N,Zwijsen A.The epicardium obscures interpretations on endothelial-to-mesenchymal transition in the mouse atrioventricular canal explant assay[J].Sci Rep,2018,8(1):4722.
[21]Cai Z,Shen L,He B,et al.Moving with and beyond cantos:how to put out the fire of inflammation in atherosclerosis[J].Int J Cardiol,2015,195:45-47.
[22]Wu M,Peng Z,Zu C,et al.Losartan attenuates myocardial endothelial-to-mesenchymal transition in spontaneous hypertensive rats via inhibiting TGF-β/Smad signaling[J].PLoS One,2016,11(5):e0155730.
[23]Koga M,Yamauchi A,Kanaoka Y,et al.BMP4 is increased in the aortas of diabetic Apo E knockout mice and enhances uptake of oxidized low density lipoprotein into peritoneal macrophages[J].Inflamm,2013,10(1):32.
[24]Lopez D,Niu G,Huber P,et al.Tumorinduced upregulation of Twist,Snail,and Slug represses the bactivity of the human VE-cadherin promoter[J].Arch Biochem Biophys,2009,482(1-2):77-82.
[25]Mahmoud MM,Serbanovic-Canic J,Feng S,et al.Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail[J].Sci Rep,2017,7(1):3375.
[26]Mahler GJ,Farrar EJ.Inflammatory cytokines promote mesenchymal transformation in embryonic and adult valve endothelial cells[J].Arterioscler Thromb Vasc Biol,2013,33(1):121-130.
[27]Sheng X,Liu Y,Wang J,et al.HUVECs respond to low shear stress stimulation by activating Wnt/β-catenin signaling pathway[J].Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi,2017,33(12):1657-1661.
[28]Lee WJ,Park JH,Shin JU,et al.Endothelial-to-mesenchymal transition induced by Wnt 3a in keloid pathogenesis[J].Wound Repair Regen,2015,23(3):435-442.
[29]Evrard SM,Lecce L,Michelis KC,et al.Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability[J].Nat Commun,2016,7:e11853.
[30]Hill JA,Olson EN.Cardiac plasticity[J].N Engl J Med,2008,358(13):1370-1380.
[31]Correia AC,Moonen JR,Brinker MG,et al.FGF2 inhibits endothelial-mesenchymal transition through microRNA-20a-mediated repression of canonical TGF-βsignaling[J].J Cell Sci,2016,129(3):569-579.
[32]Katsura A,Suzuki HI,Ueno T,et al.MicroRNA-31 is a positive modulator of endothelial-mesenchymal transition and associated secretory phenotype induced by TGF-β[J].Genes Cells,2016,21(1):99-116.
[33]Harvald EB,Olsen AS,Frgeman NJ,et al.Autophagy in the light of sphingolipid metabolism[J].Apoptosis,2015,20(5):658-670.
[34]Grimmel M,Backhaus C,Proikas-Cezanne T,et al.WIPI-mediated autophagy and longevity[J].Cells,2015,4(2):202-217.
[35]Guo FX,Hu YW,Zheng L,et al.Shear stress in autophagy and its possible mechanisms in the process of atherosclerosis[J].DNACell Biol,2017,36(5):335-346.
[36]Lien SC,Chang SF,Lee PL,et al.Mechanical regulation of cancer cell apoptosis and autophagy:roles of bone morphogenetic protein receptor,Smad1/5,and p38MAPK[J].Biochim Biophys Acta,2013,1833(12):3124-3133.
[37]Kim J,Kundu M,Viollet B,et al.AMPK and m TOR regulate autophagy through direct phosphorylation of Ulk1[J].Nat Cell Biol,2011,13(2):132-141.
[38]Yang Q,Li X,Li R,et al.Low shear stress inhibited endothelial cell autophagy through TET2 downregulation[J].Ann Biomed Eng,2016,44(7):2218-2227.
[39]Han J,Pan XY,Xu Y,et al.Curcumin induces autophagy to protect vascular endothelial cell survival from oxidative stress damage[J].Autophagy,2012,8(5):812-825.
[40]Chen ML,Yi L,Jin X,et al.Resveratrol attenuates vascular endothelial inflammation by inducing autophagy through the c AMPsignaling pathway[J].Autophagy,2013,9(12):2033-2045.
[41]Uberti F,Lattuada D,Morsanuto V,et al.Vitamin D protects human endothelial cells from oxidative stress through the autophagic and survival pathways[J].J Clin Endocrinol Metab,2014,99(4):1367-1374.
[42]Muller C,Salvayre R,Negre-Salvayre A,et al.Oxidized LDLs trigger endoplasmic reticulum stress and autophagy:prevention by HDLs[J].Autophagy,2011,7(5):541-543.
[43]Torisu T,Torisu K,Lee IH,et al.Autophagy regulates endothelial cell processing,maturation and secretion of von Willebrand factor[J].Nat Med,2013,19(10):1281-1287.
[44]Medici D,Kalluri R.Endothelial-mesenchymal transition and its contribution to the emergence of stem cell phenotype[J].Semin Cancer Biol,2012,22(5-6):379-384.
[45]Menghini R,Casagrande V,Marino A,et al.MiR-216a:a link between endothelial dysfunction and autophagy[J].Cell Death Dis,2014,5:e1029.
[46]Sun L,Zhao M,Liu A,et al.Shear stress induces phenotypic modulation of vascular smooth muscle cells via AMPK/m TOR/ULK1-mediated autophagy[J].Cell Mol Neurobiol,2018,38(2):541-548.
[47]Wang L,Han Y,Shen Y,et al.Endothelial insulin-like growth factor-1 modulates proliferation and phenotype of smooth muscle cells induced by low shear stress[J].Ann Biomed Eng,2014,42(4):776-786.
[48]Levine B,Yuan J.Autophagy in cell death:an innocent convict[J].J Clin Inves,2005,115(10):2679-2688.
[49]Moore KJ,Koplev S,Fisher EA,et al.Macrophage trafficking,inflammatory resolution,and genomics in atherosclerosis:JACC macrophage in CVD series[J].J Am Coll Cardiol,2018,72(18):2181-2197.
[50]uimet M,Franklin V,Mak E,et al.Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase[J].Cell Metab,2011,13(6):655-667.
[51]Finn AV,Nakano M,Narula J,et al.Concept of vulnerable/unstable plaque[J].Arterioscler Thromb Vasc Biol,2010,30(7):1282-1292.
[52]Martinet W,De Meyer I,Verheye S,et al.Drug-induced macrophage autophagy in atherosclerosis:for better or worse[J].Basic Res Cardiol,2013,108(1):321.
[53]Martinet W,De Loof H,De Meyer GR,et al.m TOR inhibition:a promising strategy for stabilization of atherosclerotic plaques[J].Atherosclerosis,2014,233(2):601-607.