Pathohistological Features, Immunohistochemistry And Genetic Polymorphisms Of PECAM-1 And E-selectin In Vulnerable Plague Of Coronary Arteries And Their Relationship With Acute Coronary Syndrome

Background: Heart disease remains the leading cause of death and disability in theindustrialized nations of the world for a long time and currently in the developmentcountries. It's a controversial topic on unpredictable of pathogenesis of acute coronarysyndrome (ACS) and its high lethality. Recently the concept and diagnostic criteria ofvulnerable plague are proposed and reassessment of the role of inflammation in vulnerableplague. Recent approaches by molecular genetics have facilitated the identification ofgenetic risk factors or gene polymorphisms associated with atherosclerosis.Objectives: To observe pathohistological features of vulnerable plagues in coronaryarteries, expression of PECAM-1, E-selectin in the plagues and the relationship of geneticpolymorphism with acute coronary syndrome.Materials and methods: We selected 67 identified cases of ACS which is composed ofunstable angina, myocardial infarction and cardiogenic sudden death and 60 cases ofcontrol from about 800 cases of autopsies from 1992 to 2006 in Beijing hospital.Whereafter, (1) observed occurrence and morphological features of vulnerable plagues ofACS cases in 10 aspects such as thrombus, ratio of lipid core, the minimal thickness offibrous cap, the density of inflammatory infiltration, according to the modified AmericanHeart Association atherosclerosis classification and to the consensus document of theAmerican Heart Association in 2003. (2) detected the expression of PECAM-1 andE-selectin in the plaques by immunohistochemistry. (3) analysed genetic polymorphism ofLeu125Val of PECAM-1 and Ser128Arg of E-selectin by PCR-SSCP and PCR-RFLPrespectively.Results: (1) Morphological features: the detecting sites of big lipid core is 153(50.20%),thin fibrous cap is 187(61.31%), inflammatory infiltration is 263(86.23%), neovasculatureconformation is 217(71.15%), severe stenosis is 26(8.52%), calcification is 238(78.03%),superficial calcified nodule is 26(8.52%), fissured plaque is 12(3.93%), endothelialdenudation is 3(0.98%) and Intraplaque hemorrhage is 54(17.74%). All but endothelialdenudation are significant increased than the controls. (p＜0.01). The incidence rate ofvulnerable plaques in ACS group and the control group are 89.5% and 22.0%. There are4.07 sections of vulnerable plaques in 4.55 sections reviewed in cases of ACS averagely,with high density of inflammatory infiltration, while there are 0.85 sections of vulnerableplaques in 3.87 sections reviewed in the control cases averagely, with a mild inflammatoryinfiltration. (2) Immunohistochemical features: the expression of PECAM-1 in the intimaof the ACS group and the controls are 38 cases (76%) and 8 cases (26.67%) respectively,with significant difference; the expression of E-selectin in the intima of the ACS group is 13 cases (26%), while neither in the intima of coronary arteries nor of neovasculature incontrol group. The expressions of PECAM-1 in neovasculature and arterial luminalendothelium are 58% and 28% respectively in ACS group, with significant difference, andE-selectin are 22% and 12% respectively, with significant difference. In 41 sites ofinflammatory infiltration, the expression rates of PECAM-1 and E-selectin in inflammatorycell density of＜10,10-30 and＞30/HPF are 33.33% and 68.18%, 92.31% and 16.67%,31.81% and 23.08%, with positive correlation with inflammatory cell density. (3) Genotypedetection results: the allele frequencies of 373G:C of PECAM-1 are 51.4%:48.6%→29.1%:70.9% in ACS group and control group respectively, with significant difference.(p＜0.05). The frequencies of genotype homozygote of G/G are 21.6% and 7.0% in ACSgroup and control group respectively, with no significant difference. (p＞0.05). 4 cases(10.3%) have C/C homozygote at the genetic locus 561 of E-selectinin in ACS group, withsignificant difference. (p＜0.05). The frequencies of allele C are 16.7% and 2.3% in ACSgroup and control group, with significant difference. (p＜0.05).Conclusions: 1. It was further confirmed that the incidence of vulnerable plaque in ACSgroup was higher than in the control group, which indicated that the formation ofvulnerable plaque was an important risk factor in the development of ACS. 2. The majormorphological characteristics of vulnerable plaque are big lipid core, thin fibrous cap,inflammatory infiltration, neovascularization, severe stenosis, plaque rupture, anddegeneration, necrosis and denudation of endothelial cells, which indicated thatinflammation might be play an important role in the development of vulnerable plaque. 3.The immunohistochemical expressions of PECAM-1 and E-selectin were increased atintima in ACS group and much higher in neovasculature than in arterial luminalendothelium., and there was a tendency that the expression of the two adhesion factors hada positive correlation with the increasing of density of inflammatory cells, which indicatedthat PECAM-1 and E-selectin might be play an important role in development ofvulnerable plaque. 4. The frequencies of G alleles of C+373G (Leu125Val) of PECAM-1 inACS group were significantly higher than that in the control group which indicated that itmight be a risk factor of hereditary susceptibility in Chinese ACS patients. 5. Thefrequencies of C alleles of A561C (Ser128Arg) of E-selectin in ACS group weresignificantly higher than the control group, which also indicated that it might be a riskfactor of hereditary susceptibility in Chinese ACS patients.In conclusion, the study reconfirms that inflammatory reaction play an important rolein occurrence and development of vulnerable plaque in pathomorphology of vulnerableplaque, immunohistochemical expression and genic polymorphism of PECAM-1 andE-selectin.