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- Buvall, Lisa, 1976, et al.
(författare)
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Phenotype of early cardiomyopathic changes induced by active immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the human beta-adrenergic receptor
- 2006
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Ingår i: Clin Exp Immunol. - : Oxford University Press (OUP). - 0009-9104. ; 143:2, s. 209-15
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Tidskriftsartikel (refereegranskat)abstract
- In the failing human heart, due to idiopathic dilated cardiomyopathy, it has been suggested that the beta1-adrenergic receptor (beta1AR) is a potential pathogenic autoantigen. The aim of the present study was to investigate whether immunization of rats with a synthetic peptide corresponding to the second extracellular loop of the beta1AR (beta1AR EC(II)) was able to induce the early stage of cardiomyopathy and also to investigate immunological and receptor functional parameters at a transcriptional level to permit insights into the autoimmune mechanism in cardiomyopathy. Eleven Whistar Fur rats were immunized with a beta1AR EC(II) peptide (H26R) once a month during 12 months and seven control rats were injected with vehicle according to the same procedure used for the immunized group. Cardiac function, beta1AR autoantibodies and their functional effects on cardiomyocytes were analysed. beta1AR receptor signalling, immunological and cardiomyocyte stretch markers were determined on transcriptional level. In H26R immunized rats, beta1AR autoantibodies were shown to be present and functionally active, cardiac functions in terms of fractional shortening were decreased and beta1-adrenergic receptor kinase (GRK2) mRNA were increased compared with the control group. These data have shown that immunization of rats with a putative antigenic peptide was able to induce an early stage phenotype of cardiomyopathy in the form of cardiac dysfunction and up-regulation of GRK2 as the first step in the desensitization process of the beta1AR, implying the pathological importance of the beta1AR autoantibody.
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| 2. |
- Chen, Jie, et al.
(författare)
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Effects of autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy on neonatal rat cardiomyocytes
- 2006
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Ingår i: The European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 8:5, s. 460-467
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Immunoadsorption has been shown to improve cardiac performance and reduce mortality in patients with dilated cardiomyopathy. In this study, the underlying mechanism for these beneficial effects was investigated in cultured rat cardiomyocytes. METHODS AND RESULTS: Immunoadsorption was performed in patients with dilated cardiomyopathy (n=7). Antibody-induced complement-dependent cytotoxicity was investigated by colorimetric MTT. Autoantibodies against the beta(1)-adrenoceptor were detected by ELISA and purified. Column eluent from six patients exhibited a cytotoxic effect, three patients were positive for the beta(1)-adrenoceptor autoantibodies. The purified autoantibodies were able to visualize the beta(1)-adrenoceptors by immunocytofluorescence on rat cardiomyocytes, and also displayed partial agonist properties and induced a positive chronotropic effect, which were blocked by the beta(1)-selective antagonist bisoprolol and the peptide corresponding to the beta(1)-adrenoceptor. Column eluent from one patient induced apoptosis in nick end labelling test (8.1+/-1.7% vs. 2.9+/-1.2% in control, p<0.05). CONCLUSION: Autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy have a pathophysiological role, as shown by the complement-dependent cytotoxicity and chronotropic action on rat cardiomyocytes. This implies that removal of circulating autoantibodies might be part of the underlying mechanism for improved cardiac function.
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| 3. |
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| 5. |
- Fu, J., et al.
(författare)
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Trends in graded precipitation in China from 1961 to 2000
- 2008
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Ingår i: Advances in atmospheric Sciences. - : Springer Science and Business Media LLC. - 1861-9533 .- 0256-1530. ; 25:2, s. 267-278
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Tidskriftsartikel (refereegranskat)abstract
- Daily precipitation rates observed at 576 stations in China from 1961 to 2000 were classified into six grades of intensity, including trace (no amount), slight (<= 1 mm d(-1)), small, large, heavy, and very heavy. The last four grades together constitute the so called effective precipitation (> 1 mm d(-)1). The spatial distribution and temporal trend of the graded precipitation days are examined. A decreasing trend in trace precipitation days is observed for the whole of China, except at several sites in the south of the middle section of the Yangtze River, while a decreasing trend in slight precipitation days only appears in eastern China. The decreasing trend and interannual variability of trace precipitation days is consistent with the warming trend and corresponding temperature variability in China for the same period, indicating a possible role played by increased surface air temperature in cloud formation processes. For the effective precipitation days, a decreasing trend is observed along the Yellow River valley and for the middle reaches of the Yangtze River and Southwest China, while an increasing trend is found for Xinjiang, the eastern Tibetan Plateau, Northeast China and Southeast China. The decreasing trend of effective precipitation days for the middle-lower Yellow River valley and the increasing trend for the lower Yangtze River valley are most likely linked to anomalous monsoon circulation in East China. The most important contributor to the trend in effective precipitation depends upon the region concerned.
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| 6. |
- Haugen, Espen, 1973, et al.
(författare)
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Parallel gene expressions of IL-6 and BNP during cardiac hypertrophy complicated with diastolic dysfunction in spontaneously hypertensive rats.
- 2007
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 115:1, s. 24-8
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing evidence showing that inflammation is involved in heart failure. However, heart failure may differ greatly due to different aetiologies. The role of inflammation in hypertensive heart failure, particularly in the early stage of cardiac dysfunction, has not been studied completely. This study aims at finding out whether inflammation is involved in the early stage of heart dysfunction due to hypertension. METHODS: Ten spontaneously hypertensive rats (SHR) and ten age-matched Wistar rats were used. Cardiac morphology and function, as well as coronary flow reserve, were examined by echocardiography. mRNAs for cytokines and brain natriuretic peptide were determined by RT-PCR. RESULTS: The results demonstrate cardiac hypertrophy with increased heart/body weight ratio in SHR. Echocardiographic examination has shown that SHR developed diastolic heart dysfunction as determined by tissue Doppler without decrease in systolic function. In heart biopsies, there were increased mRNA levels for interleukin-6 and brain natriuretic peptide whereas decreased mRNA for interleukin-2, beta adrenergic receptor, interferon and NFkb in SHR as compared to WKY group. Coronary flow remained unchanged in both groups. CONCLUSION: SHR developed cardiac hypertrophy complicated with diastolic heart dysfunction with increased expression of brain natriuretic peptide, down-regulation of beta adrenergic receptors and simultaneous up-regulation of IL-6, which indicates active proinflammatory process as, at least partly, underlying mechanism during the early stage when cardiac hypertrophy associated with diastolic dysfunction occurs.
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