The double edge of anti-CD40 siRNA therapy: It increases renal microcapillar density but favours the generation of an inflammatory milieu in the kidneys of ApoE −/− mice

Autor: Miguel Hueso, Angela Casas, Adrian Mallén, Laura de Ramón, Nuria Bolaños, Cristian Varela, Josep M. Cruzado, Joan Torras, Estanislao Navarro
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Journal of Inflammation, Vol 16, Iss 1, Pp 1-9 (2019)
Druh dokumentu: article
ISSN: 1476-9255
DOI: 10.1186/s12950-019-0228-9
Popis: Abstract Background Chronic kidney disease (CKD) is associated with endothelial dysfunctions thus prompting links between microcirculation (MC), inflammation and major cardiovascular risk factors. Purpose of the study We have previously reported that siRNA-silencing of CD40 (siCD40) reduced atherosclerosis (ATH) progression. Here, we have deepened on the effects of the siCD40 treatment by evaluating retrospectively, in stored kidneys from the siCD40 treated ApoE−/− mice, the renal microcirculation (measured as the density of peritubular capillaries), macrophage infiltration and NF-κB activation. Methods Kidneys were isolated after 16 weeks of treatment with the anti-CD40 siRNA (siCD40), with a scrambled control siRNA (siSC) or with PBS (Veh. group). Renal endothelium, infiltrating macrophages and activated NF-κB in endothelium were identified by immunohistochemistry, while the density of stained peritubular capillaries was quantified by image analysis. Results ATH was associated with a reduction in renal MC, an effect reversed by the anti-CD40 siRNA treatment (3.8 ± 2.7% in siCD40; vs. 1.8 ± 0.1% in siSC; or 1.9 ± 1.6% in Veh.; p
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