Encapsulated pheochromocytoma cells secrete potent noncatecholamine factors.
Encapsulated pheochromocytoma cells secrete potent noncatecholamine factors.
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封装的嗜铬细胞瘤细胞分泌有效的非儿茶酚胺因子。
DOI：
10.1089/ten.tea.2008.0412
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发表时间：
2009
影响因子：
--
通讯作者：
Edelman,ElazerR
中科院分区：
文献类型：
--
作者：
Mobine,HectorR;EngelmayrJr,GeorgeC;Moussazadeh,Nelson;Anwar,TayybaR;Freed,LisaE;Edelman,ElazerR
嗜铬细胞瘤被广泛认为是通过分泌过多的儿茶酚胺，包括去甲肾上腺素（NE）诱导心肌病。NE可具有直接的心肌细胞毒性和/或可刺激继发于高血压诱导的心肌重塑。然而，心肌病的发展并不完全与儿茶酚胺剂量或高血压的程度有关。为了探索这些作用，我们设计了一种聚合物包封系统来控制体外和体内PC 12细胞动力学和NE释放。原代新生大鼠心肌细胞与嗜铬细胞瘤条件培养基孵育显示出更大的细胞骨架的变化比单独与相同剂量的NE培养的心肌细胞，包括结蛋白，β-微管蛋白，和黏着斑蛋白和肌营养不良蛋白的上调更深刻的剂量依赖性降低。在给定NE释放水平下，心肌细胞收缩性增加29 ± 6%。琼脂糖包裹的PC 12细胞在体内保持细胞活力和结构完整性。与释放等量NE的泵相比，这些植入物诱导的心脏增大程度高30%。在体内观察微囊化细胞或NE泵植入28天后体外培养的蛋白质水平的变化。总之，这些数据表明，嗜铬细胞瘤诱导的心肌病不仅仅是一个儿茶酚胺介导的事件，相反，这种扩张型心肌病的发病机制似乎是依赖于次要因素未经审查的日期。
Pheochromocytomas are widely believed to induce cardiomyopathy via hypersecretion of catecholamines, including norepinephrine (NE). NE can have direct cardiomyocyte toxicity and/or can stimulate myocardial remodeling secondary to the induction of hypertension. Yet, the development of cardiomyopathy is not entirely related to catecholamine dose or the extent of hypertension. To explore these effects, we engineered a polymeric encapsulation system to control PC12 cell kinetics and NE releasein vitroandin vivo. Primary neonatal rat cardiomyocytes incubated with pheochromocytoma-conditioned media exhibited greater cytoskeletal changes than myocytes cultured with identical doses of NE alone, including more profound dose-dependent decreases in desmin, β-tubulin, and vinculin and upregulation of dystrophin. Cardiomyocyte contractility was 29 ± 6% greater at given levels of NE release. Agarose-encapsulated PC12 cells retain cell viability and structural integrityin vivo. These implants induce a 30% greater degree of cardiac enlargement as compared to pumps releasing equivalent doses of NE. Protein level alterations observedin vitrowere mirroredin vivoafter implantation of encapsulated cells or NE pumps for 28 days. Together, these data suggest that pheochromocytoma-induced cardiomyopathy is not solely a catecholamine-mediated event; rather, the pathogenesis of this dilated cardiomyopathy appears to be dependent upon secondary factors unexamined to date.