Interleukin 6 mediates myocardial fibrosis, concentric hypertrophy, and diastolic dysfunction in rats.
Interleukin 6 mediates myocardial fibrosis, concentric hypertrophy, and diastolic dysfunction in rats.
复制标题
DOI：
10.1161/hypertensionaha.109.148635
复制
发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Brower GL
中科院分区：
文献类型：
--
作者：
Meléndez GC;McLarty JL;Levick SP;Du Y;Janicki JS;Brower GL
虽然高血压与IL-6水平之间存在相关性，但这种细胞因子在心肌重塑中的确切作用尚不清楚。在许多高血压实验模型中报告的组织和循环中IL-6水平的变化使情况变得复杂。因此，我们探讨了IL-6水平升高介导不良心肌重构的假设。为此，将成年雄性Sprague Dawley大鼠通过渗透微型泵注射IL-6 (2.5 μg·kg-1·hr-1， IP) 7 d，并与同龄对照进行对照。左心室功能评价采用血液灌注离体心脏制备。此外，还评估了心肌间质胶原体积分数和离体心肌细胞大小。分离成人心脏成纤维细胞实验，以确定可溶性IL-6受体在介导心脏纤维化中的重要性。体内IL-6输注导致左心室同心圆肥大，心室僵硬度增加，胶原体积分数显著增加（6.2 vs. 1.7%, p < 0.001），心肌细胞宽度和长度成比例增加；这些都与血压无关。可溶性IL-6受体与IL-6联合被发现在增加分离的心脏成纤维细胞调节的胶原含量中是必不可少的，并且在介导向肌成纤维细胞的表型转化中也起作用。这些新的观察结果表明，IL-6诱导的心肌表型几乎与高血压心脏的表型相同，这表明IL-6在这一重塑过程中可能很重要。
While there is a correlation between hypertension and levels of IL-6, the exact role of this cytokine in myocardial remodeling is unknown. This is complicated by the variable tissue and circulating levels of IL-6 reported in numerous experimental models of hypertension. Accordingly, we explored the hypothesis that elevated levels of IL-6 mediate adverse myocardial remodeling. To this end, adult male Sprague Dawley rats were infused with IL-6 (2.5 μg·kg-1·hr-1, IP) for 7 days via osmotic minipump and compared to vehicle infused aged-matched controls. Left ventricular function was evaluated using a blood-perfused isolated heart preparation. In addition, myocardial interstitial collagen volume fraction and isolated cardiomyocyte size were also assessed. Isolated adult cardiac fibroblast experiments were performed to determine the importance of the soluble IL-6 receptor in mediating cardiac fibrosis. IL-6 infusions in vivo resulted in concentric left ventricular hypertrophy, increased ventricular stiffness, a marked increase in collagen volume fraction (6.2 vs. 1.7%; p < 0.001), and proportional increases in cardiomyocyte width and length; all independent of blood pressure. The soluble IL-6 receptor in combination with IL-6 was found to be essential in increasing collagen content regulated by isolated cardiac fibroblasts, and also played a role in mediating a phenotypic conversion to myofibroblasts. These novel observations demonstrate that IL-6 induces a myocardial phenotype almost identical to that of the hypertensive heart, identifying IL-6 as potentially important in this remodeling process.