ArticleJournal of inflammation (London, England)2019
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
Article in Journal of inflammation (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages' transition into a pro-inflammatory state.Cardiovascular research · 2023Article
- Article
- The CD40-CD40L Dyad as Immunotherapeutic Target in Cardiovascular Disease.Journal of cardiovascular translational research · 2021Review
- Chronic Kidney Disease-Associated Inflammation Increases the Risks of Acute Kidney Injury and Mortality after Cardiac Surgery.International journal of molecular sciences · 2020Article
- CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease.Journal of clinical medicine · 2020Review
- CD40/CD40L and Related Signaling Pathways in Cardiovascular Health and Disease-The Pros and Cons for Cardioprotection.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChronic 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
methodsKidneys 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.
resultsATH 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.;
conclusionsAnti-CD40 siRNA therapy significantly increased the density of peritubular capillaries and decreased renal inflammation in the ATH model. These data provide a physiological basis for the development of renal diseases in patients with ATH. Furthermore, our results also highligth renal off-target effects of the siRNA treatment which are discussed. GRAPHICAL ABSTRACT:
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