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The Metabolic Changes And Significance Of The Cardiolipin In Different Chronic Diseases`

Posted on:2014-10-31Degree:MasterType:Thesis
Country:ChinaCandidate:X L ShenFull Text:PDF
GTID:2254330401975743Subject:Internal Medicine
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BackgroundDiabetes mellitus is a kind of metabolic disorder which is characterized by chronichyperglycemia due to a variety of pathogenesis. But the cardiovascular disease caused by type2diabetesmellitus, especially coronary heart disease is the main complications and causes of death. Diabetesmellitus, obesity and coronary heart disease have a common pathological feature, for exemple oxidativestress and mitochondrial degeneration, etc. Cardiolipin metabolism disorders, docosahexaenoic acid incardiolipin enriched in mitochondria led to mitochondrial dysfunction, which have attracted the attentionof domestic and foreign experts and scholars on mitochondrial degeneration, cardiolipin metabolism andthe enzyme of regulating cardiolipin remodeling. In recent years, Acyl-CoA: lysocardiolipinacyltransferase-1of regulating pathological remodeling of cardiolipin has become the new entry point toreveal the pathogenesis of diabetes mellitus causing coronary heart disease and cardiomyopathy.Nearly all the cardiolipin are located in the inner mitochondrial membrane. The mitochondrialis extremely rich in the myocardial cells, Cardiolipin remodeling is also believed to play an importantrole in repairing damage of the function of myocardial cells from oxidative stress. Studies suggested thatpathological cardiolipin remodeling has happened to patients with diabetes mellitus and obesity. Inaddition, aberrant CL species were commonly found in the myocardium of patients with coronary heartdisease, ALCAT1is a key enzyme that regulates pathological remodeling of cardiolipin and leads toaberrant CL. ALCAT1is mainly located at the mitochondria-associated ER membrane, MAM is amembrane bridge between the ER and mitochondria, where ALCAT1expression level is the highest inheart and liver. ALCAT1upregulated by diet-induced obesity in a rat model, leading to mitochondrialdysfunction in cell, ROS production increased, and insulin resistance, but ALCAT1knockout mice donot occur to obesity and diabetes mellitus. Today, the study of ALCAT1mostly limited to animalexperiments in a foreign country, and is almost blank in China. It will have important significance ifthese mechanisms could be verified and elucidated in the myocardium of diabetic patients and patientswith coronary heart disease, and reveal the mechanism of Diabetes mellitus complicated with heartcomplications. ObjectiveDetecting the expression of ALCAT1mRNA in the Right auricle of patients with simplecoronary heart disease, diabetes mellitus without coronary heart disease and diabetes mellitus withcoronary heart disease, comparing their similarities and differences, exploring the metaboliccharacteristics of cardiolipin in type2diabetes mellitus and the pathogenesis of myocardial injury causedby diabetes mellitus and coronary heart disease.Methods1. The research object: Group A rheumatic heart disease17cases; Group B type2diabetesmellitus with rheumatic heart disease7cases; Group C coronary heart disease14cases; Group D type2diabetes mellitus with coronary heart disease13cases.2. Myocardial biopsy: collecting biopsy right atrial appendage tissue of a grain of rice incardiac surgery.3. Real-time reverse transcriptase-polymerase chain reaction was performed to detect theexpression ALCAT1mRNA of right atrial appendage tissue.Results(1) Group B(Group type2diabetes mellitus with rheumatic heart disease) compared withgroup A (Group rheumatic heart disease), the expression level of ALCAT1mRNA was higher in groupB than group A, it turned out that there were significant differences(Group A0.029+0.005;Group B0.039+0.004;P<0.05).(2) Group D(Group type2diabetes mellitus with coronary heart disease) compared with groupC (Group coronary heart disease), the expression level of ALCAT1mRNA was higher in group D thangroup C, there were obvious differences(Group C0.036+0.005;Group D0.043+0.004;P<0.05).(3) Group C(Group coronary heart disease) compared with group A (Group coronary heartdisease), the expression level of ALCAT1mRNA was higher in group C than group A, there weresignificant differences(Group C0.036+0.005;Group A0.029+0.005;P<0.05).Conclusion (1) Type2diabetes mellitus and coronary heart disease have a Cardiolipin metabolismdisorders.(2) Superposition of type2diabetes mellitus and coronary heart disease aggravated cardiolipinmetabolism disorders, the mechanism is a high ALCAT1mRNA expression level in in the myocardialcells.
Keywords/Search Tags:Diabetes mellitus, Acyl-CoA, lysocardiolipin acyltransferase-1, Cardiolipin remodeling
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