摘要
目的探讨胶原基因(COL3A1、COL1A2)单核苷酸多态性与脑梗死及动脉粥样硬化斑块的相关性。
方法采用病例对照研究设计,严格按准入及排除标准收集湘雅三医院住院脑梗死患者作为脑梗死组,并根据颈动脉彩超检查结果分为稳定斑块组和易损斑块组两个亚组,另选年龄和性别与脑梗死组匹配的健康者作为对照组,各研究对象之间无任何血缘关系。详细询问各研究对象的病史并记录其检查检验结果,抽取其清晨空腹静脉血,采用DNA提取试剂盒提取基因组DNA,运用聚合酶链反应-限制性酶切片段长度多态性(PCR-RFLP)方法检测研究对象COL3A1基因rs1800255位点及COL1A2基因rs42524位点多态性,分析其与脑梗死、颈动脉内膜中层厚度(CIMT)、颈动脉斑块类型的相关性。
结果
1. COL3A1基因rsl800255位点各基因型在脑梗死组和对照组之间的分布有显著性差异(P<0.05),A等位基因携带者(AA+AG)与GG基因型者在脑梗死组和对照组之间分布有显著性差异(P<0.05),但是A、G等位基因频率在两组间分布无显著性差异(P>0.05),经过二元非条件logistic回归分析未发现该位点任何一种基因型能增加或减少脑梗死的发病风险(P>0.05)；
2. COL3A1基因rsl800255位点各基因型和等位基因频率在不同CIMT水平的分布无显著性差异(P>0.05)：
3. COL3A1基因rs1800255位点各基因型及基因频率在脑梗塞不同斑块性质亚组及对照组间分布有显著性差异(P<0.05),且logistic回归分析发现该位点AA基因型使易损斑块发生风险增加(P<0.05)；
4. COL1A2基因rs42524位点各基因型和等位基因频率在脑梗死组和对照组之间分布无显著性差异(P>0.05),且二元非条件logistic回归分析未发现任何该位点一种基因型能增加或减少脑梗死发生的风险(P>0.05)；
5. COL1A2基因rs42524位点各基因型和等位基因频率在不同CIMT水平的分布无显著性差异(P>0.05)；
6. COL1A2基因rs42524位点各基因型和等位基因频率在脑梗死稳定斑块亚组和易损斑块亚组及对照组间的分布不存在统计学差异(P>0.05),二元非条件logistic回归分析未发现该位点任一种基因型增加或减少易损斑块的发生风险(P>0.05)。
结论
1.COL3A1基因rs1800255多态性与中国湖南地区汉族人群中脑梗死的发病相关,脑梗死发病可能与rs1800255位点AA/AG基因型有关,但rs1800255多态性不是脑梗死发生的独立危险因素,rs1800255位点多态性与颈动脉内膜中层厚度水平不相关,rs1800255位点AA基因型可能是颈动脉易损斑块发生的一个危险因素；
2. COL1A2基因rs42524多态性与中国湖南地区汉族人群中脑梗死的发病不相关,rs42524多态性与颈动脉内膜中层厚度水平不相关,rs42524位点多态性与颈动脉易损斑块的发生风险无关。
Objective To clarify the suspended association of the collagen gene(COL3A1, COLlA2) polymorphisms with cerebral infarction and to discuss the relationship between polymorphisms of collagen gene and onset risk of atherosclerotic plaque.
Methods Case control study was performed in this study. We collected cerebral infarction patients as CI group, which was divided into stable plaque subgroup and vulnerable subgroup according to carotid ultrasound examination. Then we chose healthy individuals as the control group,whose ages and sexes were matched with the CI group. There were no relationships among the subjects. We collected the case history and recorded the examination results seriously. We draw fasting venous blood from every subject early in the morning and obtained DNA from the blood sample using Blood DNA Kit. PCR-RFLP was used to detect the polymorphisms of COL3A1-SNP-rs1800255and COLlA2-SNP-rs42524of all subjects. Association of the collagen gene (rs1800255, rs42524) polymorphisms with cerebral infarction, carotid intima-media thickness and onset risk of carotid stable plaque, vulnerable plaque was analyzed.
Results
1.The genotypic distribution of rs1800255had significant differences between the CI group and the control group (P<0.05), and had significant differences between the A allele (AA+AG) carriers and the GG genetype carriers for rs1800255(P<0.05), but the allelic distributions of rs1800255had no significant differences between the CI group and the control group (P>0.05). Logistic regression analysis showed that any genotypes of rs1800255could not increase the risk of the onset of CI (P>0.05).
2.The genotypic and allelic distributions of rs1800255had no significant differences between different CIMT level subgroups (P>0.05).
3.The genetypic and allelic distribution of rs1800255had significant differences between the stable plaque, vunerable plaque subgroups and the control group (P<0.05). Logistic regression analysis showed that AA genotype could increase the risk of the onset of vunerable plaque (P<0.05).
4.The genotypic and allelic distribution of rs42524had no significant differences between the CI group and the control group (P>0.05). Logistic regression analysis showed that any genotypes of rs42524could not increase the risk of the onset of CI (P>0.05).
5.The genotypic and allelic distributions of rs42524had no significant differences between different CIMT level subgroups (P>0.05).
6.The genetypic and allelic distribution of rs42524had no significant differences between the vunerable plaque, stable plaque and control groups (P>0.05). Logistic regression analysis showed that any genotypes of rs42524could not increase the risk of the onset of vunerable plaque (P>0.05).
Conclusion
1. Association of rs1800255polymorphisms with cerebral infarction in Hunan Han Population may exit. AA/AG genotype of rs1800255may play promoting actor for the onset of cerebral infarction, but it is not an independent risk factor for the onset of cerebral infarction. No association of rs1800255polymorphisms with CIMT levels exists. The AA genetype of the rs180255may be a risk factor for the formation of carotid vulnerable plaque in Hunan Han Population.
2. Association of the rs42524polymorphisms with cerebral infarction in Hunan Han Population may not exist. No association of rs42524polymorphisms with CIMT levels exists. The polymorphism of rs42524has nothing to do with onset risk of carotid stable plaque or vulnerable plaque.
引文
[1]Mukherjee D, Patil CG. Epidemiology and the global burden of stroke[J]. World Neurosurg,2011;76:S85-90.
[2]Strong K, Mathers C, Bonita R. Preventing stroke:saving lives around the world[J]. Lancet Neurol,2007;6:182-7.
[3]Lopez AD, Mathers CD, Ezzati M, et al. Global and regional burden of disease and risk factors,2001:systematic analysis of population health data[J]. Lancet, 2006;367:1747-57.
[4]O'Donnell MJ, Xavier D, Liu L, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study):a case-control study[J]. Lancet,2010;376:112-23.
[5]Bak S, Gaist D, Sindrup SH, et al. Genetic liability in stroke:a long-term follow-up study of Danish twins[J]. Stroke,2002;33:769-74.
[6]中国脑卒中医疗质量评估协作组.中国急性缺血性脑卒中治疗现状[J].中华神经科杂志,2009；42：223-8.
[7]Halliday A, Mansfield A, Marro J, et al. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms:randomised controlled trial[J]. Lancet,2004;363:1491-502.
[8]Stansby G, Macdonald S, Allison R, et al. Asymptomatic carotid disease and cardiac surgery consensus[J]. Angiology,2011;62:457-60.
[9]Wang H, Ma, A, Lei, X, et al. The experimental study of relation between type I collagen, NF-KB, VCAM-1 and atherosclerosis[J]. Journal of US-China medical science,2006;3:15-9.
[10]Chen J, Zhu Y, Jiang Y, et al. A functional variant of the collagen type III alphal gene modify risk of sporadic intracranial aneurysms[J]. Hum Genet, 2012;131:1137-43.
[11]Liu W, Pang B, Lu M, et al. The rs42524 COL1A2 polymorphism is associated with primary intracerebral hemorrhage in a Chinese population[J]. J Clin Neurosci,2012;19:1711-4.
[12]Niu H, Cao Y, Wang X, et al. Relationships between hemorrhage, angioarchitectural factors and collagen of arteriovenous malformations[J]. Neurosci Bull,2012;28:595-605.
[13]Barnes MJ, Farndale RW. Collagens and atherosclerosis[J]. Exp Gerontol, 1999;34:513-25.
[14]van den Oord SC, Sijbrands EJ, Ten Kate GL, et al. Carotid intima-media thickness for cardiovascular risk assessment:Systematic review and meta-analysis[J]. Atherosclerosis,2013;228:1-11.
[15]Cuspidi C, Mancia G, Ambrosioni E, et al. Left ventricular and carotid structure in untreated, uncomplicated essential hypertension:results from the Assessment Prognostic Risk Observational Survey (APROS)[J]. J Hum Hypertens, 2004; 18:891-6.
[16]Mead GE, Murray H, Farrell A, et al. Pilot study of carotid surgery for acute stroke[J]. Br J Surg,1997;84:990-2.
[17]Rothwell PM, Warlow CP. Low risk of ischemic stroke in patients with reduced internal carotid artery lumen diameter distal to severe symptomatic carotid stenosis:cerebral protection due to low poststenotic flow? On behalf of the European Carotid Surgery Trialists' Collaborative Group[J]. Stroke,2000;31:622-30.
[18]Falk E. Morphologic features of unstable atherothrombotic plaques underlying acute coronary syndromes[J]. Am J Cardiol,1989;63:114E-20E.
[19]Falk E, Nakano M, Bentzon JF, et al. Update on acute coronary syndromes: the pathologists' view[J]. Eur Heart J,2013;34:719-28.
[20]Polak JF, Szklo M, Kronmal RA, et al. The value of carotid artery plaque and intima-media thickness for incident cardiovascular disease:the multi-ethnic study of atherosclerosis[J]. J Am Heart Assoc,2013;2:e000087.
[21]Kitamura A, Iso H, Imano H, et al. Carotid intima-media thickness and plaque characteristics as a risk factor for stroke in Japanese elderly men[J]. Stroke, 2004;35:2788-94.
[22]Kratky RG, Ivey J, Roach MR. Local changes in collagen content in rabbit aortic atherosclerotic lesions with time[J]. Atherosclerosis,1999; 143:7-14.
[23]Lee RT, Grodzinsky AJ, Frank EH, et al. Structure-dependent dynamic mechanical behavior of fibrous caps from human atherosclerotic plaques[J]. Circulation, 1991;83:1764-70.
[24]Wang KY, Tanimoto A, Sasaguri Y. Extracellular matrix and atherosclerosis[J]. J UOEH,2010;32:195-203.
[25]Muckian C, Fitzgerald A, O'Neill A, et al. Genetic variability in the extracellular matrix as a determinant of cardiovascular risk:association of type III collagen COL3A1 polymorphisms with coronary artery disease[J]. Blood, 2002; 100:1220-3.
[26]朱海霞,曾赵军,资晓宏,等.Ⅲ型胶原基因COL3A1多态性与脑梗死的相关性[J].中华神经科杂志,2007；40：444-6.
[27]Holaj R, Spacil J, Petrasek J, et al. Intima-media thickness of the common carotid artery is the significant predictor of angiographically proven coronary artery disease[J]. Can J Cardiol,2003; 19:670-6.
[28]Johnsen SH, Mathiesen EB. Carotid plaque compared with intima-media thickness as a predictor of coronary and cerebrovascular disease[J]. Curr Cardiol Rep, 2009; 11:21-7.
[29]Weis-Muller BT, Huber R, Spivak-Dats A, et al. Symptomatic acute occlusion of the internal carotid artery:reappraisal of urgent vascular reconstruction based on current stroke imaging[J]. J Vasc Surg,2008;47:752-9; discussion 9.
[30]Wong M, Edelstein J, Wollman J, et al. Ultrasonic-pathological comparison of the human arterial wall. Verification of intima-media thickness [J]. Arterioscler Thromb, 1993; 13:482-6.
[31]Shah PK. Screening asymptomatic subjects for subclinical atherosclerosis: can we, does it matter, and should we[J]? J Am Coll Cardiol,2010;56:98-105.
[32]Lorenz MW, Markus HS, Bots ML, et al. Prediction of clinical cardiovascular events with carotid intima-media thickness:a systematic review and meta-analysis[J]. Circulation,2007; 115:459-67.
[33]朱玉方,庞琦.Ⅲ型胶原蛋白COL3A1基因多态性与颅内动脉瘤的关系[J].中国脑血管病杂志,2008；5：560-2.
[34]Hua T, Zhang D, Zhao YL, et al. Correlation of COL3A1 gene with type III collagen stability in intracranial aneurysm[J]. Zhonghua Yi Xue Za Zhi,2008;88:445-8.
[35]Host NB, Aldershvile J, Horslev-Petersen K, et al. Serum aminoterminal propeptide of type III procollagen after cardiac transplantation and the effect of rejection[J]. Am J Cardiol,1996;78:1406-10.
[36]Purushothaman KR, Purushothaman M, Muntner P, et al. Inflammation, neovascularization and intra-plaque hemorrhage are associated with increased reparative collagen content:implication for plaque progression in diabetic atherosclerosis[J]. Vasc Med,2011;16:103-8.
[37]Thim T, Hagensen MK, Bentzon JF, et al. From vulnerable plaque to atherothrombosis[J]. J Intern Med,2008;263:506-16.
[38]Virmani R, Burke AP, Farb A, et al. Pathology of the vulnerable plaque[J]. J Am Coll Cardiol,2006;47:C13-8.
[39]Leikina E, Mertts MV, Kuznetsova N, et al. Type I collagen is thermally unstable at body temperature[J]. Proc Natl Acad Sci USA,2002;99:1314-8.
[40]Yoneyama T, Kasuya H, Onda H, et al. Collagen type I alpha2 (COL1A2) is the susceptible gene for intracranial aneurysms[J]. Stroke,2004;35:443-8.
[41]Moriguchi M, Yamada M, Yanagisawa T. Immunocytochemistry of keratan sulfate proteoglycan and dermatan sulfate proteoglycan in porcine tooth-germ dentin[J]. Anat Sci Int,2004;79:145-51.
[42]Viguet-Carrin S, Garnero P, Delmas PD. The role of collagen in bone strength[J]. Osteoporos Int,2006; 17:319-36.
[43]Lindahl K, Rubin CJ, Brandstrom H, et al. Heterozygosity for a coding SNP in COL1A2 confers a lower BMD and an increased stroke risk[J]. Biochem Biophys Res Commun,2009;384:501-5.
[1]Libby P. Inflammation in atherosclerosis[J]. Arterioscler Thromb Vase Biol, 2012;32:2045-51.
[2]Stansby G, Macdonald S, Allison R, et al. Asymptomatic carotid disease and cardiac surgery consensus[J]. Angiology,2011;62:457-60.
[3]Kitamura A, Iso H, Imano H, et al. Carotid intima-media thickness and plaque characteristics as a risk factor for stroke in Japanese elderly men[J]. Stroke, 2004;35:2788-94.
[4]Yla-Herttuala S, Bentzon JF, Daemen M, et al. Stabilisation of atherosclerotic plaques. Position paper of the European Society of Cardiology (ESC) Working Group on atherosclerosis and vascular biology[J]. Thromb Haemost,2011;106:1-19.
[5]Wang KY, Tanimoto A, Sasaguri Y. Extracellular matrix and atherosclerosis[J]. J UOEH,2010;32:195-203.
[6]Wang H, Ma, A, Lei, X, et al. The experimental study of relation between type I collagen, NF-KB, VCAM-1 and atherosclerosis[J]. Journal of US-China medical science,2006;3:15-9.
[7]Shekhonin BV, Domogatsky SP, Idelson GL, et al. Relative distribution of fibronectin and type Ⅰ, Ⅲ, Ⅳ, Ⅴ collagens in normal and atherosclerotic intima of human arteries[J]. Atherosclerosis,1987;67:9-16.
[8]Murata K, Motayama T, Kotake C. Collagen types in various layers of the human aorta and their changes with the atherosclerotic process[J]. Atherosclerosis, 1986;60:251-62.
[9]Purushothaman KR, Purushothaman M, Muntner P, et al. Inflammation, neovascularization and intra-plaque hemorrhage are associated with increased reparative collagen content:implication for plaque progression in diabetic atherosclerosis[J]. Vasc Med,2011;16:103-8.
[10]Barnes MJ, Farndale RW. Collagens and atherosclerosis[J]. Exp Gerontol, 1999;34:513-25.
[11]Xu H, Bihan D, Chang F, et al. Discoidin domain receptors promote alphalbetal-and alpha2betal-integrin mediated cell adhesion to collagen by enhancing integrin activation[J]. PLoS One,2012;7:e52209.
[12]Fu HL, Valiathan RR, Arkwright R, et al. Discoidin Domain Receptors: Unique Receptor Tyrosine Kinases in Collagen-mediated Signaling[J]. J Biol Chem, 2013;288:7430-7.
[13]Corti R, Hutter R, Badimon JJ, et al. Evolving concepts in the triad of atherosclerosis, inflammation and thrombosis[J]. J Thromb Thrombo lysis, 2004; 17:35-44.
[14]Schoenhagen P, Tuzcu EM, Ellis SG. Plaque vulnerability, plaque rupture, and acute coronary syndromes:(multi)-focal manifestation of a systemic disease process[J]. Circulation,2002; 106:760-2.
[15]Ogita M, Miyauchi K, Morimoto T, et al. Association between circulating matrix metalloproteinase levels and coronary plaque regression after acute coronary syndrome-subanalysis of the JAPAN-ACS study[J]. Atherosclerosis,2013;226:275-80.
[16]Xu X, Wang L, Xu C, et al. Variations in matrix metalloproteinase-1,-3, and-9 genes and the risk of acute coronary syndrome and coronary artery disease in the Chinese Han population[J]. Coron Artery Dis,2013;24:259-65.
[17]Kuzuya M, Nakamura K, Sasaki T, et al. Effect of MMP-2 deficiency on atherosclerotic lesion formation in apoE-deficient mice[J]. Arterioscler Thromb Vasc Biol,2006;26:1120-5.
[18]Choi ET, Collins ET, Marine LA, et al. Matrix metalloproteinase-9 modulation by resident arterial cells is responsible for injury-induced accelerated atherosclerotic plaque development in apolipoprotein E-deficient mice[J]. Arterioscler Thromb Vasc Biol,2005;25:1020-5.
[19]de Nooijer R, Verkleij CJ, von der Thusen JH, et al. Lesional overexpression of matrix metalloproteinase-9 promotes intraplaque hemorrhage in advanced lesions but not at earlier stages of atherogenesis[J]. Arterioscler Thromb Vasc Biol,2006;26:340-6.
[20]Silence J, Lupu F, Collen D, et al. Persistence of atherosclerotic plaque but reduced aneurysm formation in mice with stromelysin-1 (MMP-3) gene inactivation[J]. Arterioscler Thromb Vasc Biol,2001;21:1440-5.
[21]Lemaitre V, O'Byrne TK, Borczuk AC, et al. ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis[J]. J Clin Invest,2001; 107:1227-34.
[22]Luttun A, Lutgens E, Manderveld A, et al. Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein E-deficient mice against atherosclerotic media destruction but differentially affects plaque growth[J]. Circulation, 2004;109:1408-14.
[23]Deguchi JO, Aikawa E, Libby P, et al. Matrix metalloproteinase-13 collagenase-3 deletion promotes collagen accumulation and organization in mouse atherosclerotic plaques[J]. Circulation,2005; 112:2708-15.
[24]Gomez D, Owens GK. Smooth muscle cell phenotypic switching in atherosclerosis[J]. Cardiovasc Res,2012;95:156-64.
[25]Liu SQ, Teft BJ, Zhang LQ, et al. Elastic laminae in vascular development and disease[J]. Mol Cell Biomech,2010;7:59-76.
[26]Smith EB. The influence of age and atherosclerosis on the chemistry of aortic intima collagen and mucopolysaccharides[J]. J Atheroscler Res,1965;5:241-8..
[27]Koyama H, Raines EW, Bornfeldt KE, et al. Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors[J]. Cell, 1996;87:1069-78.
[28]Tanner FC, Boehm M, Akyurek LM, et al. Differential effects of the cyclin-dependent kinase inhibitors p27(Kipl), p21(Cip1), and p16(Ink4) on vascular smooth muscle cell proliferation[J]. Circulation,2000;101:2022-5.
[29]Li S, Lao J, Chen BP, et al. Genomic analysis of smooth muscle cells in 3-dimensional collagen matrix[J]. FASEB J,2003;17:97-9.
[30]Tanner FC, Yang ZY, Duckers E, et al. Expression of cyclin-dependent kinase inhibitors in vascular disease[J]. Circ Res,1998;82:396-403.
[31]Hollenbeck ST, Itoh H, Louie O, et al. Type I collagen synergistically enhances PDGF-induced smooth muscle cell proliferation through pp60src-dependent crosstalk between the alpha2betal integrin and PDGFbeta receptor[J]. Biochem Biophys Res Commun,2004;325:328-37.
[32]Plenz G, Dorszewski A, Breithardt G, et al. Expression of type VIII collagen after cholesterol diet and injury in the rabbit model of atherosclerosis[J]. Arterioscler Thromb Vasc Biol,1999;19:1201-9.
[33]Hou G, Mulholland D, Gronska MA, et al. Type ⅤⅢ collagen stimulates smooth muscle cell migration and matrix metalloproteinase synthesis after arterial injury[J]. Am J Pathol,2000; 156:467-76.
[34]Adiguzel E, Hou G, Mulholland D, et al. Migration and growth are attenuated in vascular smooth muscle cells with type ⅤⅢ collagen-null alleles[J]. Arterioscler Thromb Vasc Biol,2006;26:56-61.
[35]Hou G, Vogel W, Bendeck MP. The discoidin domain receptor tyrosine kinase DDR1 in arterial wound repair[J]. J Clin Invest,2001; 107:727-35.
[36]Franco C, Hou G, Ahmad PJ, et al. Discoidin domain receptor 1 (DDR1) deletion decreases atherosclerosis by accelerating matrix accumulation and reducing inflammation in low-density lipoprotein receptor-deficient mice[J]. Circ Res, 2008; 102:1202-11.
[37]Ichii T, Koyama H, Tanaka S, et al. Fibrillar collagen specifically regulates human vascular smooth muscle cell genes involved in cellular responses and the pericellular matrix environment[J]. Circ Res,2001;88:460-7.
[38]Kanda S, Kuzuya M, Ramos MA, et al. Matrix metalloproteinase and alphavbeta3 integrin-dependent vascular smooth muscle cell invasion through a type Ⅰ collagen lattice[J]. Arterioscler Thromb Vase Biol,2000;20:998-1005.
[39]Stringa E, Knauper V, Murphy G, et al. Collagen degradation and platelet-derived growth factor stimulate the migration of vascular smooth muscle cells[J]. J Cell Sci,2000;113 (Pt 11):2055-64.
[40]Carragher NO, Levkau B, Ross R, et al. Degraded collagen fragments promote rapid disassembly of smooth muscle focal adhesions that correlates with cleavage of pp125(FAK), paxillin, and talin[J]. J Cell Biol,1999;147:619-30.
[41]Jones PL, Jones FS, Zhou B, et al. Induction of vascular smooth muscle cell tenascin-C gene expression by denatured type I collagen is dependent upon a beta3 integrin-mediated mitogen-activated protein kinase pathway and a 122-base pair promoter element[J]. J Cell Sci,1999;112 (Pt 4):435-45.
[42]Siasos G, Tousoulis D, Kioufis S, et al. Inflammatory mechanisms in atherosclerosis:the impact of matrix metalloproteinases[J]. Curr Top Med Chem, 2012; 12:1132-48.
[43]Wesley RB,2nd, Meng X, Godin D, et al. Extracellular matrix modulates macrophage functions characteristic to atheroma:collagen type I enhances acquisition of resident macrophage traits by human peripheral blood monocytes in vitro[J]. Arterioscler Thromb Vasc Biol,1998; 18:432-40.
[44]Gudewicz PW, Frewin MB, Heinel LA, et al. Priming of human monocyte superoxide production and arachidonic acid metabolism by adherence to collagen-and basement membrane-coated surfaces[J]. J Leukoc Biol,1994;55:423-9.
[45]Schapira K, Lutgens E, de Fougerolles A, et al. Genetic deletion or antibody blockade of alpha1 beta1 integrin induces a stable plaque phenotype in ApoE-/-mice[J]. Arterioscler Thromb Vasc Biol,2005;25:1917-24.
[46]Gowen BB, Borg TK, Ghaffar A, et al. The collagenous domain of class A scavenger receptors is involved in macrophage adhesion to collagens[J]. J Leukoc Biol, 2001;69:575-82.
[47]Gowen BB, Borg TK, Ghaffar A, et al. Selective adhesion of macrophages to denatured forms of type I collagen is mediated by scavenger receptors[J]. Matrix Biol, 2000;19:61-71.
[48]Kamohara H, Yamashiro S, Galligan C, et al. Discoidin domain receptor 1 isoform-a (DDR1alpha) promotes migration of leukocytes in three-dimensional collagen lattices[J]. FASEB J,2001; 15:2724-6.
[49]Franco C, Britto K, Wong E, et al. Discoidin domain receptor 1 on bone marrow-derived cells promotes macrophage accumulation during atherogenesis[J]. Circ Res,2009; 105:1141-8.