Study On The Mechanism Of Adipose Tissue Endocrine Disfunction In Coronary Atherosclerosis And Cyanotic Congenital Heart Diseases

Part1Correlation between epicardial adipose tissue adipokines expression of Coronary Artery disease patients and endoplasmic reticulum stressObjective: To investigate the correlation between epicardial adipose tissue adipokine expression of Coronary Artery disease (CAD) patients and endoplasmic reticulum stress.Methods Choose coronary heart disease and heart valve surgery patients a total of106patients, including52cases in Coronary Artery disease group, Valvular heart disease group of54, after the narcotic induction took peripheral venous blood, epicardial adipose tissue were collected when cardiovascular surgery. Acording to Gensini's score, coronary lesions of coronary heart disease group were devided into three groups:<30group,30to90group,>90group. The serum concentration of Adiponectin TNF-α, IL-10were measured with the use of an enzyme-linked immunosorbent assay (ELISA) assay, Real-time quantitative PCR(RT-PCR) was used to analysis adipokines mRNA level, Western blot method was used to detect adiponectin and inflammatory markER Stress P-NF k BP65, P-IkBα, JNK and P-JNK and the endoplasmic reticulum stress indicator of GRP78protein expression. Results Serum adiponectin concentration in coronary heart disease group serum adiponectin was lower than the valvular disease group (P<0.05), TNF-aand IL-10have no significantly difference. With the increase of coronary lesions degree in Coronary heart disease group, serum adiponectin was decreased; RT-PCR and Western blot method to detect adiponectin of epicardial adipose tissue, with coronary lesions degree increase, adiponectin expression was also decreased (P<0.05).The endoplasmic reticulum stress and inflammation-related indicators increased as opposed to the valvular disease group (P<0.05).The endoplasmic reticulum stress inducER Stress can induce these changes.Conclusion The expression of adiponectin was decreased in coronary heart disease epicardial adipose tissue and inflammatory factors were increased.With coronary lesions degree increase, adiponectin expression was also decreased.The change were related to the induction endoplasmic reticulum stress. Part2Adipose tissue hypoxia and endocrine dysfunction caused by cyanosis congenital heart diseaseObjective: To investigated the effects of hypoxia induced by CCHD on the expression and secretion of adipokines..Methods:Subcutaneous adipose tissue and serum were obtained from elective cardiac surgery patients. In CCHD group, n=17; and in ACHD(Acyanosis congenital heart disease) group, n=15.Vascular endothelial growth factor (VEGF), inflammation-related adipokines, adiponectin (APN) and Endoplasmic reticulum stress (ER Stress) markER Stress were measured in mRNA levels. Hypoxia inducible factor1a (HIF-1a) and ER Stress markER Stress were also measured in protein levels.Results: Immunohistochemical staining showed that protein expression levels of VEGF was markedly increased relative to acyanotic groups. Adipose tissue was hypoxic in cyanotic groups. Adipose tissue hypoxia (ATH) led to a substantial increase in inflammation-related adipokines, and a remarkable reduction in adiponectin mRNA levels. Endoplasmic reticulum stress markER Stress were activated by hypoxia. ER stress has linked to inflammation. These changes were partially revER Stressed by the intervention of normoxia. We exposed normal adipose tissue to CoCl2, a hypoxia mimic, and achieved results similar to the CCHD group. Conclusion: Adipose tissue in CCHD is hypoxic. The change of adiponectin and inflammation-related adipokines are partially caused by ER stress.