Roman-Campos Danilo, Duarte Hugo Leonardo L, Sales Policarpo A, Natali Antonio J, Ropert Catherine, Gazzinelli Ricardo T, Cruz Jader S
Dept. of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Basic Res Cardiol. 2009 May;104(3):238-46. doi: 10.1007/s00395-009-0776-x. Epub 2009 Feb 3.
Trypanosoma cruzi, an intracellular protozoan parasite infecting a wide variety of vertebrates, is the agent responsible for Chagas' disease. This pathology often results in severe inflammatory heart condition and it is one of the major causes of dilated cardiomyopathy leading to heart failure in Latin America. Nevertheless, little is known about the changes in isolate cardiac myocytes contractility during the development of this pathology. Here we report a relationship between cytokines profile of mice infected with T. cruzi and the modifications in the cellular contractility pattern. We found that cellular contractility, measured as fractional shortening, showed a complex behavior. The changes were evaluated during the acute phase (15, 30 and 45 dpi) and chronic phase (>90 dpi). The time to half contraction and relaxation were lengthier despite the number of days after infection or the heart region evaluated. The maximal contraction and relaxation velocities were significantly slower. The observed changes in cellular contractility were correlated with the presence of circulating IFN-gamma, TNF-alpha and MCP-1/CCL2 during the course of infection. Together, our data demonstrate that cellular contractility is altered in the three heart regions studied, and these alterations are observed at the very beginning of the parasitism and they remained until the chronic phase has been reached. Indeed, we propose a role for IFN-gamma, TNF-alpha and MCP-1/CCL2 in the mechanical heart remodeling during experimental Chagas' disease.
克氏锥虫是一种感染多种脊椎动物的细胞内原生动物寄生虫，是恰加斯病的病原体。这种病症常导致严重的炎症性心脏病，是拉丁美洲导致扩张型心肌病进而引发心力衰竭的主要原因之一。然而，对于这种病症发展过程中分离的心肌细胞收缩性的变化却知之甚少。在此，我们报告了感染克氏锥虫的小鼠细胞因子谱与细胞收缩模式改变之间的关系。我们发现，以缩短分数衡量的细胞收缩性表现出复杂的行为。在急性期（感染后15、30和45天）和慢性期（感染后>90天）对这些变化进行了评估。尽管感染天数或评估的心脏区域不同，但半数收缩和舒张时间更长。最大收缩和舒张速度明显较慢。观察到的细胞收缩性变化与感染过程中循环中的干扰素-γ、肿瘤坏死因子-α和单核细胞趋化蛋白-1/CCL2的存在相关。总之，我们的数据表明，在所研究的三个心脏区域中细胞收缩性发生了改变，并且这些改变在寄生虫感染的最初阶段就已出现，并一直持续到进入慢性期。事实上，我们提出干扰素-γ、肿瘤坏死因子-α和单核细胞趋化蛋白-1/CCL2在实验性恰加斯病期间心脏机械重塑中发挥作用。
