整联蛋白调控血管新生内膜增生的研究进展
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摘要
血管新生内膜增生是支架植入术、动静脉瘘术等血管手术以及动脉粥样硬化、高血压等心血管疾病的生理特征。整联蛋白介导的细胞黏附在新生内膜增生过程中起着重要作用。该文概述了整联蛋白在此过程中对白细胞黏附、平滑肌细胞迁移增殖、再内皮化的调控及目前用于研究新生内膜的相关动物模型。了解整联蛋白调节血管新生内膜增生的分子机制,为临床上防治新生内膜增生、解决术后血管再狭窄等相关研究提供参考。
Neointimal hyperplasia is a major morphological feature of many cardiovascular diseases such as atherosclerosis and hypertension, it is also responsible for the stenosis of vascular surgery including stent angioplasty and arteriovenous fistula surgery. Integrin-mediated cell adhesion plays a very important role in neointimal hyperplasia development. We reveiwed here the effect of integrin on neointimal formation through regulating leucocyte adhesion, smooth muscle cell proliferation and migration, reendothelialization as well as the frequently used animal model of neointimal hyperplasia. Understanding the mechanisms of neointimal hyperplasia modulated by integrin will provide new therapeutic strategies for these clinical diseases.
Neointimal hyperplasia is a major morphological feature of many cardiovascular diseases such as atherosclerosis and hypertension, it is also responsible for the stenosis of vascular surgery including stent angioplasty and arteriovenous fistula surgery. Integrin-mediated cell adhesion plays a very important role in neointimal hyperplasia development. We reveiwed here the effect of integrin on neointimal formation through regulating leucocyte adhesion, smooth muscle cell proliferation and migration, reendothelialization as well as the frequently used animal model of neointimal hyperplasia. Understanding the mechanisms of neointimal hyperplasia modulated by integrin will provide new therapeutic strategies for these clinical diseases.
引文
1 Ahanchi SS,Tsihlis ND,Kibbe MR.The role of nitric oxide in the pathophysiology of intimal hyperplasia.J Vasc Surg 2007;45Suppl A:A64-73.
2 Tian DY,Jin XR,Zeng X,Wang Y.Notch signaling in endothelial cells:is it the therapeutic target for vascular neointimal hyperplasia?Int J Mol Sci 2017;doi:10.3390/ijms18081615.
3 Hynes RO.Integrins:bidirectional,allosteric signaling machines.Cell 2002;110(6):673-87.
4 Kotha J,Zhang C,Longhurst CM,Lu Y,Jacobs J,Cheng Y,et al.Functional relevance of tetraspanin CD9 in vascular smooth muscle cell injury phenotypes:a novel target for the prevention of neointimal hyperplasia.Atherosclerosis 2009;203(2):377-86.
5 Daniel JM,Penzkofer D,Teske R,Dutzmann J,Koch A,Bielenberg W,et al.Inhibition of miR-92a improves reendothelialization and prevents neointima formation following vascular injury.Cardiovasc Res 2014;103(4):564-72.
6 Ley K,Laudanna C,Cybulsky MI,Nourshargh S.Getting to the site of inflammation:the leukocyte adhesion cascade updated.Nat Rev Immunol 2007;7(9):678-89.
7 Tseng CN,Chang YT,Lengquist M,Kronqvist M,Hedin U,Eriksson EE.Platelet adhesion on endothelium early after vein grafting mediates leukocyte recruitment and intimal hyperplasia in a murine model.Thromb Haemost 2015;113(4):813-25.
8 Inoue T,Sakai Y,Morooka S,Hayashi T,Takayanagi K,Takabatake Y.Expression of polymorphonuclear leukocyte adhesion molecules and its clinical significance in patients treated with percutaneous transluminal coronary angioplasty.JAm Coll Cardiol 1996;28(5):1127-33.
9 Inoue T,Sohma R,Miyazaki T,Iwasaki Y,Yaguchi I,Morooka S.Comparison of activation process of platelets and neutrophils after coronary stent implantation versus balloon angioplasty for stable angina pectoris.Am J Cardiol 2000;86(10):1057-62.
10 Du L,Qu X,Zheng H,Li R,Wang J,Chen M,et al.Reverse apolipoprotein A-I mimetic peptide R-D4F inhibits neointimal formation following carotid artery ligation in mice.Am J Pathol2013;182(5):1932-9.
11 Lodish H,Berk A,Matsudaira P,Kaiser C,Krieger M,Scott MP,et al.Molecular Cell Biology,5 th ed.New York:Worth Publisher,2004,197-244.
12 Chung CH,Lin KT,Chang CH,Peng HC,Huang TF.The integrin alpha2beta1 agonist,aggretin,promotes proliferation and migration of VSMC through NF-kB translocation and PDGFproduction.Br J Pharmacol 2009;156(5):846-56.
13 Pan L,Zhao Y,Yuan Z,Qin G.Research advances on structure and biological functions of integrins.Springerplus 2016;5(1):1094.
14 Hibbert B,Ma X,Pourdjabbar A,Holm E,Rayner K,Chen YX,et al.Inhibition of endothelial progenitor cell glycogen synthase kinase-3beta results in attenuated neointima formation and enhanced re-endothelialization after arterial injury.Cardiovasc Res 2009;83(1):16-23.
15 Schroeter MR,Leifheit M,Sudholt P,Heida NM,Dellas C,Rohm I,et al.Leptin enhances the recruitment of endothelial progenitor cells into neointimal lesions after vascular injury by promoting integrin-mediated adhesion.Circ Res 2008;103(5):536-44.
16 Alberts B,Johnson A,Lewis,J,Morgan D,Raff M,Roberts K,et al.Molecular Biology of the Cell,Sixth ed.New York:Garland Science,Taylor&Francis Group,2014,1074-90.
17 Welser JV,Lange N,Singer CA,Elorza M,Scowen P,Keef KD,et al.Loss of the alpha7 integrin promotes extracellular signalregulated kinase activation and altered vascular remodeling.Circ Res 2007;101(7):672-81.
18 Wang L,Zheng J,Du Y,Huang Y,Li J,Liu B,et al.Cartilage oligomeric matrix protein maintains the contractile phenotype of vascular smooth muscle cells by interacting with alpha(7)beta(1)integrin.Circ Res 2010;106(3):514-25.
19 Zargham R,Pepin J,Thibault G.alpha8beta1 Integrin is upregulated in the neointima concomitant with late luminal loss after balloon injury.Cardiovasc Pathol 2007;16(4):212-20.
20 Zargham R,Thibault G.Alpha 8 integrin expression is required for maintenance of the smooth muscle cell differentiated phenotype.Cardiovasc Res 2006;71(1):170-8.
21 Menendez-Castro C,Cordasic N,Neureiter D,Amann K,Marek I,Volkert G,et al.Under-expression of alpha8 integrin aggravates experimental atherosclerosis.J Pathol 2015;236(1):5-16.
22 Takada Y,Ye X,Simon S.The integrins.Genome Biol 2007;8(5):215.
23 Wainwright CL,Miller AM,Wadsworth RM.Inflammation as a key event in the development of neointima following vascular balloon injury.Clin Exp Pharmacol Physiol 2001;28(11):891-5.
24 Wu H,Gower RM,Wang H,Perrard XY,Ma R,Bullard DC,et al.Functional role of CD11c+monocytes in atherogenesis ass ociated with hypercholesterolemia.Circulation 2009;119(20):2708-17.
25 Kokubo T,Uchida H,Choi ET.Integrin alpha(v)beta(3)as a target in the prevention of neointimal hyperplasia.J Vasc Surg2007;45 Suppl A:A33-8.
26 Choi ET,Khan MF,Leidenfrost JE,Collins ET,Boc KP,Villa BR,et al.Beta3-integrin mediates smooth muscle cell accumulation in neointima after carotid ligation in mice.Circulation 2004;109(12):1564-9.
27 Jiang H,Lun Y,Wu X,Xia Q,Zhang X,Xin S,et al.Association between the hypomethylation of osteopontin and integrin beta3promoters and vascular smooth muscle cell phenotype switching in great saphenous varicose veins.Int J Mol Sci 2014;15(10):18747-61.
28 Liang M,Wang Y,Liang A,Dong JF,Du J,Cheng J.Impaired integrin beta3 delays endothelial cell regeneration and contributes to arteriovenous graft failure in mice.Arterioscler Thromb Vasc Biol 2015;35(3):607-15.
29 Bandyopadhyay A,Raghavan S.Defining the role of integrin alphavbeta6 in cancer.Curr Drug Targets 2009;10(7):645-52.
30 Inoue T,Uchida T,Yaguchi I,Sakai Y,Takayanagi K,Morooka S.Stent-induced expression and activation of the leukocyte integrin Mac-1 is associated with neointimal thickening and restenosis.Circulation 2003;107(13):1757-63.
31 Shimazawa M,Kondo K,Hara H,Nakashima M,Umemura K.Sulfatides,L-and P-selectin ligands,exacerbate the intimal hyperplasia occurring after endothelial injury.Eur J Pharmacol2005;520(1/2/3):118-26.
32 Li G,Sanders JM,Bevard MH,Sun Z,Chumley JW,Galkina EV,et al.CD40 ligand promotes Mac-1 expression,leukocyte recruitment,and neointima formation after vascular injury.Am JPathol 2008;172(4):1141-52.
33 Zago AC,Simon DI,Wang Y,Sakuma M,Chen Z,Croce K,et al.The importance of the interaction between leukocyte integrin Mac-1 and platelet glycoprotein Ib-a for leukocyte recruitment by platelets and for the inflammatory response to vascular injury.Arq Bras Cardiol 2008;90(1):54-63.
34 Flintoff-Dye NL,Welser J,Rooney J,Scowen P,Tamowski S,Hatton W,et al.Role for the alpha7beta1 integrin in vascular development and integrity.Dev Dyn 2005;234(1):11-21.
35 Zargham R,Wamhoff BR,Thibault G.RNA interference targeting alpha8 integrin attenuates smooth muscle cell growth.FEBS Lett 2007;581(5):939-43.
36 Sheu JR,Wu CH,Chen YC,Hsiao G,Lin CH.Mechanisms in the inhibition of neointimal hyperplasia with triflavin in a rat model of balloon angioplasty.J Lab Clin Med 2001;137(4):270-8.
37 Wu CH,Chen YC,Hsiao G,Lin CH,Liu CM,Sheu JR.Mechanisms involved in the inhibition of neointimal hyperplasia by abciximab in a rat model of balloon angioplasty.Thromb Res2001;101(3):127-38.
38 Coleman KR,Braden GA,Willingham MC,Sane DC.Vitaxin,a humanized monoclonal antibody to the vitronectin receptor(alphavbeta3),reduces neointimal hyperplasia and total vessel area after balloon injury in hypercholesterolemic rabbits.Circ Res 1999;84(11):1268-76.
39 Han M,Wen JK,Zheng B,Liu Z,Chen Y.Blockade of integrin beta3-FAK signaling pathway activated by osteopontin inhibits neointimal formation after balloon injury.Cardiovasc Pathol2007;16(5):283-90.
40 Schlosser A,Pilecki B,Hemstra LE,Kejling K,Kristmannsdottir GB,Wulf-Johansson H,et al.MFAP4 promotes vascular smooth muscle migration,proliferation and accelerates neointima formation.Arterioscler Thromb Vasc Biol 2016;36(1):122-33.
41 Caplice NM,Wang S,Tracz M,Croatt AJ,Grande JP,Katusic ZS,et al.Neoangiogenesis and the presence of progenitor cells in the venous limb of an arteriovenous fistula in the rat.Am JPhysiol Renal Physiol 2007;293(2):F470-5.
42 Werner N,Nickenig G.Influence of cardiovascular risk factors on endothelial progenitor cells:limitations for therapy?Arterioscler Thromb Vasc Biol 2006;26(2):257-66.
43 Fujiyama S,Amano K,Uehira K,Yoshida M,Nishiwaki Y,Nozawa Y,et al.Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells.Circ Res 2003;93(10):980-9.
44 Nelson J,Wu Y,Jiang X,Berretta R,Houser S,Choi E,et al.Hyperhomocysteinemia suppresses bone marrow CD34+/VEGF receptor 2+cells and inhibits progenitor cell mobilization and homing to injured vasculature-a role of beta1-integrin in progenitor cell migration and adhesion.FASEB J 2015;29(7):3085-99.
45 Shih YT,Wang MC,Yang TL,Zhou J,Lee DY,Lee PL,et al.beta(2)-Integrin and Notch-1 differentially regulate CD34(+)CD31(+)cell plasticity in vascular niches.Cardiovasc Res 2012;96(2):296-307.
46 Jeremy JY,Thomas AC.Animal models for studying neointima formation.Curr Vasc Pharmacol 2010;8(2):198-219.
47 Brahmbhatt A,Remuzzi A,Franzoni M,Misra S.The molecular mechanisms of hemodialysis vascular access failure.Kidney Int2016;89(2):303-16.
48 Wang Y,Liang A,Luo J,Liang M,Han G,Mitch WE,et al.Blocking Notch in endothelial cells prevents arteriovenous fistula failure despite CKD.J Am Soc Nephrol 2014;25(4):773-83.
2 Tian DY,Jin XR,Zeng X,Wang Y.Notch signaling in endothelial cells:is it the therapeutic target for vascular neointimal hyperplasia?Int J Mol Sci 2017;doi:10.3390/ijms18081615.
3 Hynes RO.Integrins:bidirectional,allosteric signaling machines.Cell 2002;110(6):673-87.
4 Kotha J,Zhang C,Longhurst CM,Lu Y,Jacobs J,Cheng Y,et al.Functional relevance of tetraspanin CD9 in vascular smooth muscle cell injury phenotypes:a novel target for the prevention of neointimal hyperplasia.Atherosclerosis 2009;203(2):377-86.
5 Daniel JM,Penzkofer D,Teske R,Dutzmann J,Koch A,Bielenberg W,et al.Inhibition of miR-92a improves reendothelialization and prevents neointima formation following vascular injury.Cardiovasc Res 2014;103(4):564-72.
6 Ley K,Laudanna C,Cybulsky MI,Nourshargh S.Getting to the site of inflammation:the leukocyte adhesion cascade updated.Nat Rev Immunol 2007;7(9):678-89.
7 Tseng CN,Chang YT,Lengquist M,Kronqvist M,Hedin U,Eriksson EE.Platelet adhesion on endothelium early after vein grafting mediates leukocyte recruitment and intimal hyperplasia in a murine model.Thromb Haemost 2015;113(4):813-25.
8 Inoue T,Sakai Y,Morooka S,Hayashi T,Takayanagi K,Takabatake Y.Expression of polymorphonuclear leukocyte adhesion molecules and its clinical significance in patients treated with percutaneous transluminal coronary angioplasty.JAm Coll Cardiol 1996;28(5):1127-33.
9 Inoue T,Sohma R,Miyazaki T,Iwasaki Y,Yaguchi I,Morooka S.Comparison of activation process of platelets and neutrophils after coronary stent implantation versus balloon angioplasty for stable angina pectoris.Am J Cardiol 2000;86(10):1057-62.
10 Du L,Qu X,Zheng H,Li R,Wang J,Chen M,et al.Reverse apolipoprotein A-I mimetic peptide R-D4F inhibits neointimal formation following carotid artery ligation in mice.Am J Pathol2013;182(5):1932-9.
11 Lodish H,Berk A,Matsudaira P,Kaiser C,Krieger M,Scott MP,et al.Molecular Cell Biology,5 th ed.New York:Worth Publisher,2004,197-244.
12 Chung CH,Lin KT,Chang CH,Peng HC,Huang TF.The integrin alpha2beta1 agonist,aggretin,promotes proliferation and migration of VSMC through NF-kB translocation and PDGFproduction.Br J Pharmacol 2009;156(5):846-56.
13 Pan L,Zhao Y,Yuan Z,Qin G.Research advances on structure and biological functions of integrins.Springerplus 2016;5(1):1094.
14 Hibbert B,Ma X,Pourdjabbar A,Holm E,Rayner K,Chen YX,et al.Inhibition of endothelial progenitor cell glycogen synthase kinase-3beta results in attenuated neointima formation and enhanced re-endothelialization after arterial injury.Cardiovasc Res 2009;83(1):16-23.
15 Schroeter MR,Leifheit M,Sudholt P,Heida NM,Dellas C,Rohm I,et al.Leptin enhances the recruitment of endothelial progenitor cells into neointimal lesions after vascular injury by promoting integrin-mediated adhesion.Circ Res 2008;103(5):536-44.
16 Alberts B,Johnson A,Lewis,J,Morgan D,Raff M,Roberts K,et al.Molecular Biology of the Cell,Sixth ed.New York:Garland Science,Taylor&Francis Group,2014,1074-90.
17 Welser JV,Lange N,Singer CA,Elorza M,Scowen P,Keef KD,et al.Loss of the alpha7 integrin promotes extracellular signalregulated kinase activation and altered vascular remodeling.Circ Res 2007;101(7):672-81.
18 Wang L,Zheng J,Du Y,Huang Y,Li J,Liu B,et al.Cartilage oligomeric matrix protein maintains the contractile phenotype of vascular smooth muscle cells by interacting with alpha(7)beta(1)integrin.Circ Res 2010;106(3):514-25.
19 Zargham R,Pepin J,Thibault G.alpha8beta1 Integrin is upregulated in the neointima concomitant with late luminal loss after balloon injury.Cardiovasc Pathol 2007;16(4):212-20.
20 Zargham R,Thibault G.Alpha 8 integrin expression is required for maintenance of the smooth muscle cell differentiated phenotype.Cardiovasc Res 2006;71(1):170-8.
21 Menendez-Castro C,Cordasic N,Neureiter D,Amann K,Marek I,Volkert G,et al.Under-expression of alpha8 integrin aggravates experimental atherosclerosis.J Pathol 2015;236(1):5-16.
22 Takada Y,Ye X,Simon S.The integrins.Genome Biol 2007;8(5):215.
23 Wainwright CL,Miller AM,Wadsworth RM.Inflammation as a key event in the development of neointima following vascular balloon injury.Clin Exp Pharmacol Physiol 2001;28(11):891-5.
24 Wu H,Gower RM,Wang H,Perrard XY,Ma R,Bullard DC,et al.Functional role of CD11c+monocytes in atherogenesis ass ociated with hypercholesterolemia.Circulation 2009;119(20):2708-17.
25 Kokubo T,Uchida H,Choi ET.Integrin alpha(v)beta(3)as a target in the prevention of neointimal hyperplasia.J Vasc Surg2007;45 Suppl A:A33-8.
26 Choi ET,Khan MF,Leidenfrost JE,Collins ET,Boc KP,Villa BR,et al.Beta3-integrin mediates smooth muscle cell accumulation in neointima after carotid ligation in mice.Circulation 2004;109(12):1564-9.
27 Jiang H,Lun Y,Wu X,Xia Q,Zhang X,Xin S,et al.Association between the hypomethylation of osteopontin and integrin beta3promoters and vascular smooth muscle cell phenotype switching in great saphenous varicose veins.Int J Mol Sci 2014;15(10):18747-61.
28 Liang M,Wang Y,Liang A,Dong JF,Du J,Cheng J.Impaired integrin beta3 delays endothelial cell regeneration and contributes to arteriovenous graft failure in mice.Arterioscler Thromb Vasc Biol 2015;35(3):607-15.
29 Bandyopadhyay A,Raghavan S.Defining the role of integrin alphavbeta6 in cancer.Curr Drug Targets 2009;10(7):645-52.
30 Inoue T,Uchida T,Yaguchi I,Sakai Y,Takayanagi K,Morooka S.Stent-induced expression and activation of the leukocyte integrin Mac-1 is associated with neointimal thickening and restenosis.Circulation 2003;107(13):1757-63.
31 Shimazawa M,Kondo K,Hara H,Nakashima M,Umemura K.Sulfatides,L-and P-selectin ligands,exacerbate the intimal hyperplasia occurring after endothelial injury.Eur J Pharmacol2005;520(1/2/3):118-26.
32 Li G,Sanders JM,Bevard MH,Sun Z,Chumley JW,Galkina EV,et al.CD40 ligand promotes Mac-1 expression,leukocyte recruitment,and neointima formation after vascular injury.Am JPathol 2008;172(4):1141-52.
33 Zago AC,Simon DI,Wang Y,Sakuma M,Chen Z,Croce K,et al.The importance of the interaction between leukocyte integrin Mac-1 and platelet glycoprotein Ib-a for leukocyte recruitment by platelets and for the inflammatory response to vascular injury.Arq Bras Cardiol 2008;90(1):54-63.
34 Flintoff-Dye NL,Welser J,Rooney J,Scowen P,Tamowski S,Hatton W,et al.Role for the alpha7beta1 integrin in vascular development and integrity.Dev Dyn 2005;234(1):11-21.
35 Zargham R,Wamhoff BR,Thibault G.RNA interference targeting alpha8 integrin attenuates smooth muscle cell growth.FEBS Lett 2007;581(5):939-43.
36 Sheu JR,Wu CH,Chen YC,Hsiao G,Lin CH.Mechanisms in the inhibition of neointimal hyperplasia with triflavin in a rat model of balloon angioplasty.J Lab Clin Med 2001;137(4):270-8.
37 Wu CH,Chen YC,Hsiao G,Lin CH,Liu CM,Sheu JR.Mechanisms involved in the inhibition of neointimal hyperplasia by abciximab in a rat model of balloon angioplasty.Thromb Res2001;101(3):127-38.
38 Coleman KR,Braden GA,Willingham MC,Sane DC.Vitaxin,a humanized monoclonal antibody to the vitronectin receptor(alphavbeta3),reduces neointimal hyperplasia and total vessel area after balloon injury in hypercholesterolemic rabbits.Circ Res 1999;84(11):1268-76.
39 Han M,Wen JK,Zheng B,Liu Z,Chen Y.Blockade of integrin beta3-FAK signaling pathway activated by osteopontin inhibits neointimal formation after balloon injury.Cardiovasc Pathol2007;16(5):283-90.
40 Schlosser A,Pilecki B,Hemstra LE,Kejling K,Kristmannsdottir GB,Wulf-Johansson H,et al.MFAP4 promotes vascular smooth muscle migration,proliferation and accelerates neointima formation.Arterioscler Thromb Vasc Biol 2016;36(1):122-33.
41 Caplice NM,Wang S,Tracz M,Croatt AJ,Grande JP,Katusic ZS,et al.Neoangiogenesis and the presence of progenitor cells in the venous limb of an arteriovenous fistula in the rat.Am JPhysiol Renal Physiol 2007;293(2):F470-5.
42 Werner N,Nickenig G.Influence of cardiovascular risk factors on endothelial progenitor cells:limitations for therapy?Arterioscler Thromb Vasc Biol 2006;26(2):257-66.
43 Fujiyama S,Amano K,Uehira K,Yoshida M,Nishiwaki Y,Nozawa Y,et al.Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells.Circ Res 2003;93(10):980-9.
44 Nelson J,Wu Y,Jiang X,Berretta R,Houser S,Choi E,et al.Hyperhomocysteinemia suppresses bone marrow CD34+/VEGF receptor 2+cells and inhibits progenitor cell mobilization and homing to injured vasculature-a role of beta1-integrin in progenitor cell migration and adhesion.FASEB J 2015;29(7):3085-99.
45 Shih YT,Wang MC,Yang TL,Zhou J,Lee DY,Lee PL,et al.beta(2)-Integrin and Notch-1 differentially regulate CD34(+)CD31(+)cell plasticity in vascular niches.Cardiovasc Res 2012;96(2):296-307.
46 Jeremy JY,Thomas AC.Animal models for studying neointima formation.Curr Vasc Pharmacol 2010;8(2):198-219.
47 Brahmbhatt A,Remuzzi A,Franzoni M,Misra S.The molecular mechanisms of hemodialysis vascular access failure.Kidney Int2016;89(2):303-16.
48 Wang Y,Liang A,Luo J,Liang M,Han G,Mitch WE,et al.Blocking Notch in endothelial cells prevents arteriovenous fistula failure despite CKD.J Am Soc Nephrol 2014;25(4):773-83.