Background: It has been well documented over past decades that interaction of pathogens with the extracellular matrix (ECM) plays a primary role in host cell attachment and invasion. Adherence to host tissues is mediated by surface-exposed proteins expressed by the microorganisms during infection. The mechanisms by which pathogenic leptospires invade and colonize the host remain poorly understood since few virulence factors contributing to the pathogenesis of the disease have been identified. Whole-genome sequencing analysis of L. interrogans allowed identification of a repertoire of putative leptospiral surface proteins.
Chagas disease is caused by the parasite Trypanosoma cruzi, and it begins with a short acute phase characterized by high parasitemia followed by a life-long chronic phase with scarce parasitism. Cardiac involvement is the most prominent manifestation, as 30% of infected subjects will develop abnormal ventricular repolarization with myocarditis, fibrosis and cardiomyocyte hypertrophy by undefined mechanisms. Nevertheless, follow-up studies in chagasic patients, as well as studies with murine models, suggest that the intensity of clinical symptoms and pathophysiological events that occur during the acute phase of disease are associated with the severity of cardiac disease observed during the chronic phase. In the present study we investigated the role of microRNAs (miRNAs) in the disease progression in response to T. cruzi infection, as alterations in miRNA levels are known to be associated with many cardiovascular disorders. We screened 641 rodent miRNAs in heart samples of mice during an acute infection with the Colombiana T.cruzi strain and identified multiple miRNAs significantly altered upon infection. Seventeen miRNAs were found significantly deregulated in all three analyzed time points post infection. Among these, six miRNAs had their expression correlated with clinical parameters relevant to the disease, such as parasitemia and maximal heart rate-corrected QT (QTc) interval. Computational analyses identified that the gene targets for these six miRNAs were involved in networks and signaling pathways related to increased ventricular depolarization and repolarization times, important factors for QTc interval prolongation. The data presented here will guide further studies about the contribution of microRNAs to Chagas heart disease pathogenesis.
Objective-To analyse the morphological aspects of the extracellular matrix and microcirculation to clarify whether chronic Chagas' cardiopathy (CCC) is an accurate model to study the pathogenesis of idiopathic dilated cardiomyopathy (IDCM). Design-Thick histological myocardial sections were prepared to analyse collagen, and microcirculation was examined during confocal laser and light microscopy. Setting-The specimens were prepared at the pathology service of the Heart Institute of Sã o Paulo, Brazil. Patients-Nine control hearts, eight IDCM hearts, and 10 CCC hearts were studied after necropsy. Main outcome measures-The number of collagen struts per 100× field, the area of fibrosis (%), and the diameters of arterioles and capillaries were measured in each heart to establish outcome. Results-A smaller number (mean (SD)) of collagen struts was seen in the hearts in the IDCM group (9.1 (4.1)) than in the control (22.4 (3.2)) (p < 0.05) or CCC (15.7 (7.4)) (p > 0.05) groups. Fibrosis was greater in the CCC hearts (13.8 (10.5)%) than in the IDCM hearts (5.9 (6.6)%) (p > 0.05). Major increases in arteriole (65.4 (9.9) µm) and capillary (9.9 (1.7) µm) diameters were seen in the CCC hearts but not in the IDCM hearts (arteriole diameter 40.3 (7.9) µm; capillary diameter 7.9 (1.3) µm). Conclusions-Hearts demonstrating CCC and IDCM present diVerent extracellular and microvessel alterations. This suggests that distinct pathogenic mechanisms are responsible for each condition and that CCC is not an eVective model to study IDCM. (Heart 1999;82:279-285)
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