Wang Shiwen

Voltage-dependent anion channel (VDAC) is involved in apoptosis of cell lines carrying the mitochondrial DNA mutation

BackgroundThe mitochondrial voltage-dependent anion channel (VDAC) is increasingly implicated in the control of apoptosis. We have studied the effects the mitochondrial DNA (mtDNA) tRNAIle mutation on VDAC expression, localization, and apoptosis.MethodsLymphoblastoid cell lines were derived from 3 symptomatic and 1 asymptomatic members of a family with hypertension associated with the A4263G tRNAIle mutation as well as from control subjects. Mitochondrial potential (ΔΨm) and apoptosis were measured by flow cytometry; co-localization of VDAC and Bax was evaluated by confocal microscopy.ResultsExpression of VDAC and Bax in mtDNA cell lines was found to be increased compared to controls, while expression of the small conductance calcium-dependant potassium channel (sKCa) was unchanged. Confocal imaging revealed co-localization of VDAC/Bax on the outer mitochondrial membrane of A4263G cell lines but not from controls. Flow cytometry indicated that the mitochondrial potential was decreased by 32% in mutated cells versus controls while rates of apoptosis were increased (P < 0.05). The difference was attenuated by Cyclosporin A (CsA, 2 μM), a blocker of VDAC.ConclusionWe conclude that increased expression of mitochondrial VDAC and subcellular co-localization of VDAC/Bax increases mitochondrial permeability and apoptosis in cell lines carrying the mtDNA tRNAIle A4263G mutation.

Mitochondrial tRNAMet mutation in Chinese Han essential hypertensive individuals

The objective of the present study was to explore the relationship between mitochondrial tRNAMet mutation and development of essential hypertension in Chinese Han individuals. A total of 990 patients with essential hypertension were involved. The general data (sex, age, body mass index, onset age, and family history) and information on routine blood test, blood biochemical examination, and color Doppler echocardiography of these patients were collected. All subjects under-went venous blood drawing for seperating white blood cells and DNA extraction. Then, mitochondrial tRNAMet was amplified and sequenced after purification. The patients who carried the tRNAMet mutation were taken as the indicative cases and the controls were the patients with essential hypertension who did not carry the mutation. We performed a comparative analysis on the routine blood test, blood biochemical examination, color Doppler echocardiography, and other data between the indicative cases and control cases. Among the 990 essential hypertensive patients, there were 8 who carried the tRNAMet mutation, and 6 mutation sites were confirmed, including A4401G, C4410A, U4418C, A4435G, U4454C, and C4456U. Compared with the control cases, the indicative cases developed essential hypertension at earlier ages. The average levels of high density of lipoprotein cholesterol, left ventricular end diastolic diameter, stroke volume, and cardiac index were higher in the indicative cases than in the controls. While the average levels of hemoglobin and left ventricular ejection fraction were lower in the indicative cases than in the control cases. Among the 8 indicative cases, 5 had maternally inherited hyper-tension; one had paternally inherited hypertension; and two denied any family history of hypertension. These results indicated that the mitochondrial tRNAMet mutations might induce the changes in structure and function, which was involved in the progress of the essential hypertension by disturbing the blood metabolism, the steady-state of the blood cells, and the cardiac structure and function.

The effect of Xinfukang oral liquid on the expression of ND4 in rat's myocadial cell in the chronic heart failure

Objective To investigate the effect of Xinfukang Oral Liquid on the expression of ND4 mRNA and Protein of myocardial mitochondria in pressure overload-induced left ventricular hypertrophy rats. Methods Totally, 240 SD rats were randomly divided into three groups, sham operation group (SH) (n=80), coarctation of abdominal aorta model group (CAA) (n=80) and model and Xinfukang liquid treatment group (XFK) (n=80). Congestive Heart Failure rat models were made by partly coarctating the abdominal aorta of rats. Expression of ND4 mRNA and protein were observed at the fourth, eighth and 12th week after the treatment, respectively by RT-PCR and Western Blotting. Results In CAA group at the eighth week after operation, the content of ND4 mRNA and ND4 protein were both decreased compared with SH group (p<0.01); content of ND4 mRNA (p<0.01) and ND4 protein (p<0.05) in XFK group were increased compared with CAA group. And these changes were far more significant at 12 weeks. Conclusion XFK oral liquid can upregulate expression of ND4 mRNA and ND4 protein in myocardial mitochondria of pressure overload rats and improve Myocardial energy metabolism.

e0443 A new 30-day mortality risk score system for patients hospitalised with acute myocardial infarction

Objectives To derive and validate a simple scoring system that predicts risk of 30-day mortality in patients hospitalised with acute myocardial infarction (AMI). Methods We included 5, 524 patients with AMI who hospitalised from January 1, 1993, through December 31, 2009, at Chinese PLA General Hospital in Beijing. Age, sex, comorbidity, in-hospital mortality and complications were examined for patients primarily admitted for AMI. Results The 30-day in-hospital mortality was 9.2% in patients. Cox regression multivariate analysis showed that a history of stroke and the complications such as cardiac shock, heart failure, ventricular tachycardia/fibrillation, pneumonia, gastrointestinal bleeding, multiple organ dysfunction syndromes, being female and being older than 50 were the only independent predictors of in-hospital mortality. Using the regression coefficient as a benchmark, we calculated a convenient score. In the validation dataset, the 1,677 patients with the lowest scores had a mortality rate of 1.5% and the 1,454 patients with the highest scores had a mortality rate of 24.2%. Conclusions The study illustrates that a history of stroke, the complications, gender and age (older than 50) have proved to be a major prognostic marker for immediate poor outcome in the patients with AMI. The score may help to identify patients who are more likely to have a risk of in-hospital mortality within 30-days.

e0319 Predicting 30-day mortality among patients hospitalised for decompensated heart failure

Objective We investigated clinical correlates of in-hospital mortality and comorbidity of patients demonstrating heart failure progression in a large population. Methods We included 6,949 patients with demonstrating heart failure who were hospitalised from the period of January 1, 1993, to December 31, 2007, at Chinese PLA General Hospital in Beijing. Hospital mortality and comorbidities were examined for the patients primarily admitted for decompensated HF. Results The 30-day in-hospital mortality was 5.4% in patients. Cox regression multivariate analysis showed that a history of cor pulmonale, stroke, renal failure, cirrhosis of liver-myocardial infarction, pneumonia, gastrointestinal bleeding and multiple organ dysfunction syndromes and age older than 65 years were the only independent predictors of in-hospital mortality. Using the regression coefficient as a benchmark, we calculated a convenient score. Nearly 23% of the patients with the score >6 died compared with only 1.2% of the patients with the score of 0. Conclusion Medical comorbidity at admission or age older than 65 years is an independent risk factor for 30-day mortality in patients with heart failure. The study illustrates that medical comorbidities at admission have proved to be a major prognostic marker for immediate poor outcome in the patients with heart failure. The score may help to identify patients who are more likely to have a risk of in-hospital mortality within 30-days.