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A Pathophysiological Role of Growth Factors in Idiopathic Cardiomyopathy.

生长因子在特发性心肌病中的病理生理学作用。

基本信息

批准号：
06670747
负责人：
TOMITA Yoshifumi
金额：
$ 1.15万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06670747/
关键词：
growth factor FGF TGFbeta apoptosis cardiomyopathy model animal cardiac hypertrophy cardiomyopathy cardiomyocyte in situ hybridization FGF(fibroblast growth factor)

项目摘要

To clarify pathophysiological roles of FGF in idiopathic cardiomyopathy, LV endomyocardial biopsy specimens from 24 patients (9 HCM,12 DCM,and 3 hypertensive hypertrophy) and 6 controls were stained for acidic FGF (aFGF) and basic FGF using immunohistochemistry. Positive staining of acidic FGF was observed in myocytes of biopsy specimen from 15 of 21 (71%) cardiomyopathy patients, all hypertensive hypertrophy patients, but none of the controls (p<0.01 ; cardiomyopathy vs controls). Average diameter of myocytes was larger in patients with positive aFGF staining than those with negative staining. Percent area of fibrosis and capillary vessel density were not significantly different between two groups, however. intense expression of aFGF mRNA was observed in myocytes from the patients with positive aFGF protein.The findings above mentioned were further ascertained by experimental study in cardiomyopathic animals. Syrian hamster BIO14.6 (aged 6 and 20 weeks) and control hamster (F1beta) with the matched age were used (n=12). Histological examination, western blot for aFGF protein, and immunohistochemistry using polyclonal anti-human acidic FGF and oplyclonal anti-human VEGF165 were evaluated. Immunostaining revealed marked accumulation of aFGF in myocytes from BIO 14.6 hamster, especially in degenerated myocytes. Positive staining of aFGF in myocytes were observed in 6/6 of BIO 14.6 hamsters, while in 1/6 of control hamster. Western blot for aFGF protein showed 19kD band was more apparent in myocardial extract of BIO 14.6 hamster than control hamster F1beta.[Conclusion]Expression of aFGF was significantly increased in the left ventricle of human idiopathic cardiomyopathy and hamster cardiomyopathy. It is suggested that aFGF might play an important role in myocyte hypertrophy and repair response of myocardial degeneration in animal cardiomyopathy. Further study is needed to clarify whether aFGF is ameliorating or deteriorating factor in cardiomyopathy.

为了阐明 FGF 在特发性心肌病中的病理生理学作用，使用免疫组织化学对 24 名患者（9 名 HCM、12 名 DCM 和 3 名高血压肥厚）和 6 名对照者的左心室心内膜心肌活检标本进行酸性 FGF (aFGF) 和碱性 FGF 染色。在来自 21 名心肌病患者中的 15 名（71%）的活检标本的肌细胞中观察到酸性 FGF 阳性染色，所有患者均为高血压肥厚患者，但没有对照者（p<0.01；心肌病与对照）。 aFGF 染色阳性患者的肌细胞平均直径大于染色阴性患者。然而，纤维化面积百分比和毛细血管密度在两组之间没有显着差异。 aFGF蛋白阳性患者的肌细胞中观察到aFGF mRNA的强烈表达。上述结果通过心肌病动物的实验研究得到进一步证实。使用叙利亚仓鼠 BIO14.6（6 周和 20 周）和年龄匹配的对照仓鼠（F1beta）（n = 12）。对组织学检查、aFGF 蛋白的蛋白质印迹以及使用多克隆抗人酸性 FGF 和多克隆抗人 VEGF165 的免疫组织化学进行了评估。免疫染色显示 BIO 14.6 仓鼠的肌细胞中 aFGF 显着积累，尤其是退化的肌细胞中。在 6/6 的 BIO 14.6 仓鼠中观察到肌细胞中 aFGF 的阳性染色，而在对照仓鼠中为 1/6。 aFGF蛋白Western blot结果显示，BIO 14.6仓鼠心肌提取物中19kD条带较对照仓鼠F1β更为明显。【结论】人特发性心肌病和仓鼠心肌病左心室aFGF表达显着升高。提示aFGF可能在动物心肌病心肌细胞肥大和心肌退变修复反应中发挥重要作用。需要进一步研究来阐明 aFGF 是否是心肌病的改善或恶化因素。