The Study Of Hs-CRP、MMP-9、PAPP-A Relationship With Atherosclerosis Plaque Stability And Ezetimibe Intervention

Coronary atherosclerotic heart disease seriously threat to human health.Its menchanism is atherosclerosis(AS).Study shown that AS plaque ruptureand thrombosis, which is the main reason leading to acute cardiovascularevent. In the lesions leads to acute cardiovascular events，about70%is plaquerupture（including erosion，calcified nodules or plaque of other type），therefore, plaque stenosis and the risk of complication is not proportion. butrelated by plaque vulnerability. Definition of plaque vulnerability is the plaqueease of thrombosis or could quickly develop into culpris lesions. Considerableevidence show that AS is a chronic inflammatory process，but the AS plaquechronic inflammation process is key factor of plaque rupture and promoting ofACS，more active inflammatory response，more unstable plaque. Depth studyof the mechanism of plaque vulnerability and its decetion technology andintervention strategies. Make vulnerable plaque transform to stable direction，are important methods for prevention of acute cardiovascular event. This studyaimed to the following two points:1. Early identification of vulnerable plaqueby detecting serum inflammatory markers；2. Research the role of ezetimibe invulnerable plaque of anti-inflammatory.Objective：1. To explore vulnerable plaque modeling method;2.Explorethe relationship between serum inflammatory markers and plaquevulnerablility;3. To observe the influence of ezetimibe on blood lipid, plaquestability and serum inflammatory marker.Method:60newzealand white rabbits were randomly divide into3groups：blank control group（group A）,model control group（group B）,drugcontrol group（group C）,20in each group. Group A give normal diet. GroupB and C, the former with atherosclerotic-like arterial lesions will be inducedby balloon overstretch injury of the abdominal aorta. Simultaneously they were fed high cholesterol diet, group C intervened by ezetimibe, at the sametime, group B do not. All animals after12weeks fed will be carry outTC,LDL-C, hs-CRP, MMP-9,PAPP-a detection.7days latter, sacrificed all ofrabbits, abdominal artery was taken for observe plaque rupture and thrombosis.Plaque rupture based on local thrombosis, it can not be determined as plaquerupture if there was no thrombosis. After HE staining，each group randomlyselect five high power lens to pathological analysis of the thickness of thefibrous cap thickness (FCT)and the ratio of intima media thickness(IMT). Thethickness of fibrous cap and intima-media thickness ratio（FCT/IMT）、Endometrial thickness and thickness ratio（IT/MT）to determine the stability ofthe plaque. Observe the relationship of hs-CRP、MMP-9、PAPP-A plaquestability by pathological results, observe the role of ezetimibe in stabilizationplaque.Result:1. A total of14rabbits unfinished study，5rabbits died ofinfection during the experiment，9rabbits died during balloon dilatation orafter48hour. Rabbit survival after12weeks：15in A,15in B,16in C.2. After12weeks，blood lipids and serum inflammatory detection：bloodTC、LDL-C were35.45±1.86mmol/,25.45±0.77mmol/L. Compare to group A,3.32±0.39mmol/L,1.97±0.07mmol/Lwere significant increase(P<0.01). Afterezetimibe intervention, blood TC and LDL-C level were significantly lower，were17.70±1.11mmol/L,14.47±0.45mmol/L, compare to A and B significantdifferences(P<0.01). hs-CRP, MMP-9, PAPP-A in group B were238.70±23.97ug/ml,247.60±18.23pg/ml,36.56±3.65mlU/ml, compare togroup A95.85±5.09ug/ml,117.61±4.20pg/ml,20.49±2.14mlU/ml weresignificantly increase(P<0.01). After intervened by ezetimibe hs-CRP was155.47±16.08ug/ml，significantly lower to B(P <0.01)，MMP-9, PAPP-A inC were255.60±6.37pg/ml、37.78±2.99mlU/ml. Compare to B，there is nosignificant difference(P>0.05).3. Pathological result: In naked eyes，group A arterial showed intimalsmooth，no plaque rupture and thrombosis in group A，arterial intimal plaqueof group B are pale yellow protrusions.13plaques in12ones in15rabbits spontaneouly rupture with thrombus. Pale yellow plaques protrusionintegrated into one in group C,15plaques in15ones in16rabbitsspontaneouly rupture with thrombus. This indicates that vulnerable plaquemodel were developed successfully. After HE staining，aortic intima smooth，endothelial cell integrity， aortic tunica media consisted of elastic fibermembrane arranged concentrically， annular smooth muscle cells in thematrixin group A. Compared with group A，group B has significantly thinnerfibrous cap， large number of macrophage can be seen infiltrating insubendothelial. Thrombus formed in the vessel lumen，Consider cause byplaque rupture. Group C has significantly thinner fibrous cap，large number ofmacrophage can be seen infiltrating in subendothelial. Lipids and necroticmaterial accumulated in subendothelial, aoritic tunica media elastic fibermembrane structure looked unclear, cell disorder. Compare group B to C inFCT, IMT, FCT/IMT and IT/IMT, there were no statistically significantdifference(P>0.01). Compare hs-CRP, MMP-9, PAPP-A and plaque’s IMTin there groups by linear correlation analysis, three indicators were positivelycorrelated with IMT, P<0.01.Conclusion:1Balloon overstretch injury of the abdominal aorta and fedhigh cholesterol diet, could develop animal model similar to human coronaryatherosclerotic vulnerable plaque characteristics.2Three indicators werepositively correlated with IMT, Plaque vulnerability is related with seruminflammatory marker. early detect hs-CRP, MMP-9and PAPP-A can identifyvulnerable plaque, which benefit to coronary heart disease early diagnosis andtreatment, expected to be used for clinical.3Ezetimibe, as selectivecholesterol absorption inhibitor, can achieve powerful lipid-lowering effects.4Ezetimibe, as selective cholesterol absorption inhibitor，there is no significantdifference in effect to vulnerable plaque serum inflammatory marker. Nosignificant difference in FCT、IMT、FCT/IMT、IT/MT，Its anti-inflammatory effects and stabilize plaques effects need to further confirmed.