Characterization of renal microvasculature in chronic kidney disease

• Charakterisierung der renalen Mikrovaskulatur bei chronischer Nierenerkrankung

Ermert, Katja; Jankowski, Joachim (Thesis advisor); Boor, Peter (Thesis advisor)

Aachen : RWTH Aachen University (2022, 2023)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2022

Abstract

In renal fibrosis, the pathological hallmark of chronic kidney disease (CKD), peritubular capillaries undergo structural, ultrastructural and functional alterations, including increased fluid permeability and rarefaction (Bábíčková et al., 2017). Several preliminary studies indicated that alterations in the renal microvasculature include endothelial activation and endothelial dysfunction (Basile and Yoder, 2014, Verma and Molitoris, 2015). To analyse these alterations on the morphological and molecular level, a method to isolate peritubular ECs was established. The highest number of viable cells was obtained by FACS isolation of fluorophore-labeled ECs from the transgenic mice. Although it was not possible to culture these primary cells for a longer time in vitro, a direct comparison of ECs isolated from healthy and fibrotic kidneys showed increased expression of the injury marker E-selectin in cells from diseased tissue. This was confirmed by histological FISH analyses which showed E-selectin as a de novo expressed injury marker in two murine renal fibrosis models. The identification of a biomarker for vascular injury could help to diagnose or predict microvascular injury in CKD. The glycocalyx lines the luminal surface of vascular EC and impedes platelet aggregation, inflammatory cell adhesion and regulates the vascular permeability. The staining of fibrotic kidneys with LEL revealed that the EG underwent morphological changes and was reduced during progressive renal disease and fibrosis. Novel establishment of the LaDy GAGa staining method showed significant ultrastructural changes of the EG and examining the components of the EG revealed the shedding of the EG during progressive renal disease. Our data indicated that microvasculature injury and shedding of the EG is an important mechanism of progressive renal disease and might be of clinical relevance for future translational studies targeting the EG and the endothelium.

Institutions

• Department of Biology [160000]
• [531010-3]