Laboratorio de Investigación en Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru ; Asociación Benéfica PRISMA, Lima, Peru.
PLoS Negl Trop Dis. 2013;7(2):e1996. doi: 10.1371/journal.pntd.0001996. Epub 2013 Feb 7.
We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. In addition, we evaluated collagen I, III, IV (CI, CIII and CIV) deposition in cardiac tissue, and their relationship with serum levels of procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III amino-terminal propeptide (PIIINP). Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Deposition of cardiac collagen types was determined by immunohistochemistry and serum levels of PICP, PIIINP, and anti-T. cruzi IgG1 and IgG2 by ELISA. IgG2 (Th1 response) predominated throughout the course of infection; IgG1 (Th2 response) was detected during the chronic phase. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase. Cardiac levels of CI, CIII, CIV increased progressively, but the highest levels were seen in the chronic phase and were primarily due to increase in CIII and CIV. High serum levels of PICP and PIIINP were observed throughout the infection, and increased levels of both biomarkers were associated with cardiac fibrosis (p = 0.002 and p = 0.038, respectively). These results confirm the role of apoptosis in cell loss mainly during the chronic phase and the utility of PICP and PIIINP as biomarkers of fibrosis in cardiac remodeling during T. cruzi infection.
我们研究了克氏锥虫感染引起的心脏重构中的细胞凋亡和坏死。此外，我们还评估了心脏组织中 I、III、IV 型胶原（CI、CIII 和 CIV）的沉积及其与血清 I 型前胶原羧基端肽（PICP）和 III 型前胶原氨基端肽（PIIINP）水平的关系。8 只感染和 2 只未感染的豚鼠在感染后 7 个时间点进行尸检，时间长达 1 年。通过组织病理学观察和末端脱氧核苷酸转移酶 dUTP 缺口末端标记法分别确定坏死和凋亡引起的细胞死亡。通过免疫组织化学法测定心脏胶原类型的沉积，通过 ELISA 法测定血清 PICP、PIIINP、抗克氏锥虫 IgG1 和 IgG2 水平。感染过程中 IgG2（Th1 反应）占主导地位；在慢性期检测到 IgG1（Th2 反应）。在急性期，坏死引起的心脏细胞死亡多于凋亡；在慢性期，心脏细胞中观察到凋亡和坏死。淋巴细胞、内皮细胞和心外膜脂肪组织中也观察到凋亡，尤其是在慢性期。CI、CIII、CIV 的心脏水平逐渐升高，但在慢性期达到最高水平，主要是由于 CIII 和 CIV 的增加。在整个感染过程中观察到血清 PICP 和 PIIINP 水平升高，两种生物标志物水平的升高与心脏纤维化有关（p=0.002 和 p=0.038）。这些结果证实了凋亡在细胞丢失中的主要作用主要发生在慢性期，PICP 和 PIIINP 可作为克氏锥虫感染期间心脏重构纤维化的生物标志物。
