The Correlation Between Bone Related Proteins And Calcification In Coronary Atherosclerosis Plaque Through The CAMP-PKA Pathway Of Vascular Smooth Muscle Cells In Inflammatory Stress

Part one The correlation between chronic inflammation and coronary atherosclerosis on pathological analysisObjective: To explore the correlation between chronic inflammation and coronary atherosclerosis(CAS)through pathological way.Methods: Autopsy data and medical records of patients with CAS and/or chronic inflammatory diseases were analyzed retrospectively.Results: There were 216 patients with CAS accompanied with mild chronic inflammatory diseases.One hundred and fifty-nine patients were male and 57 patients were female.Left anterior descending branch was the most vulnerable part to atherosclerosis and stenosis.There were 196 patients with chronic bronchitis(CB)in CAS patients.There was a positive correlation between CB and CAS(rs=0.404,P=0.000),and chronic bronchitis was one of the risk factors of CAS(OR=4.852,95%CI=2.898 to 8.124,P=0.000),whereas other chronic inflammation,such as chronic pyelonephritis,chronic gastroenteritis,chronic esophagitis,chronic lymphocytic thyroiditis and chronic cervicitis and CAS had no significant correlation with CAS(P >0.05).Conclusion: CB is one of the risk factors for CAS.It is important to treat CB so as to decrease the incidence and mortality of coronary heart disease.Part two The correlation between bone related proteins in VSMCs and calcification in coronary atherosclerosis plaque in inflammatory stressObjective: To investigate the origin of osteoblast phenotype cells,the correlation between bone related proteins and calcification in CAS plaque by detecting the relative content of calcium salt in CAS plaque,the expression of interleukin-6(IL-6),Protein kinase A(PKA),Cyclic adenosine monophosphate-response element binding protein(CREB)and bone related proteins,such as bone gla protein(BGP),osteopontin(OPN)and Runt related transcription factor 2(RUNX2).Methods: The human CAS plaques were divided into five groups: normal group,stenosis of group I,stenosis of group II,stenosis of group III and stenosis of group IV.HE staining and special staining methods were used to examine the morphological changes of atherosclerotic plaques and analyze the relative content of calcium salt.Origin of osteoblast phenotype cells was detected by immunohistochemistry.The expression of bone related proteins in CAS plaque was detected by immunohistochemical staining and western blot.The expression of PKA and CREB in CAS plaque was detected by western blot.The correlation between IL-6 and bone related proteins was also analyzed.Results: Coronary artery calcification rate was increased with the increasing of the degree of luminal stenosis.Different levels of calcium deposition showed in stenosis of group II-IV,and there was a significant difference in these three groups(P<0.05).Origin of osteoblast phenotype cells was mainly monocyte-macrophages in early CAS plaques(stenosis group I-II),but it was vascular smooth muscle cells(VSMCs)in advanced CAS plaques(stenosis group III-IV).The expression of IL-6,BGP,OPN and RUNX2 was increased with the increasing of lumen stenosis.The expression of IL-6,BGP and RUNX2 in stenosis of group I-IV was statistical significance,compared with the normal group(P<0.01).However,OPN was significant in stenosis of group II-IV compared with the normal group(P<0.01).The expression of PKA and CREB in stenosis of group II-IV was statistically significant compared with the normal group(P<0.01).The expression of IL-6 and bone related proteins was in linear positive correlation(P<0.01).Conclusion: VSMCs in coronary artery,through the c AMP-PKA pathway mediated by inflammatory factors,could change phenotype to osteoblast and express bone related proteins,which eventually leads to calcification in CAS plaque.