Kurzfassung

CTEPH is a frequent cause of right heart failure, which develops in a subset of patients with previous pulmonary embolism. Because the pathomechanisms of this life-threatening disease are unknown, surgical removal of the obstructive thrombofibrotic material from the pulmonary arteries remains the only curative approach. We have shown that PEA lesions are composed of five histologically distinct regions consisting primarily of either fresh or organized thrombus, activated myofibroblasts,...CTEPH is a frequent cause of right heart failure, which develops in a subset of patients with previous pulmonary embolism. Because the pathomechanisms of this life-threatening disease are unknown, surgical removal of the obstructive thrombofibrotic material from the pulmonary arteries remains the only curative approach. We have shown that PEA lesions are composed of five histologically distinct regions consisting primarily of either fresh or organized thrombus, activated myofibroblasts, large, irregular vessels or fibrotic material. Analysis of venous thrombosis in mice suggested that these areas represent a time course of events from thrombus formation to resolution. However, the reasons for venous thrombus non-resolution and fibrotic remodeling in patients with CTEPH are unknown. Previous studies into the pathomechanisms of this disease may have been hampered by the fact that tissues had to be disintegrated during mRNA preparation and that gene expression analysis was performed using pooled mRNA. Using such traditional approaches, any spatial information on gene expression is lost, which might be of particular relevance given the tissue heterogeneity of CTEPH lesions. In the proposed collaborative research project between the DZHK site RheinMain and Munich, we will attempt to overcome this limitation by generating a spatial laser microdissection tomography of PEA material followed by nCounter gene expression analysis (in cooperation with SE-105) and histological validation of disease candidates. Using this novel approach, we expect to obtain important insights into the pathomechanisms underlying CTEPH.» weiterlesen» einklappen