# ILK Deletion Protects Against Chronic Kidney Disease-Associated Vascular Damage

## TL;DR

Deleting ILK in mice prevents vascular damage linked to chronic kidney disease, suggesting it could be a new treatment target.

## Contribution

This study shows that ILK depletion protects against CKD-related vascular fibrosis in mice.

## Key findings

- ILK deletion in mice prevented CKD-induced vascular fibrosis and morphological changes.
- Uremic toxins increased ILK activity and fibrosis markers in wild-type but not in ILK-depleted cells.
- Reduced ILK expression correlates with decreased fibrosis in aortas of CKD mice.

## Abstract

Cardiovascular diseases are a major cause of morbidity and mortality in chronic kidney disease (CKD) patients. Integrin-linked kinase (ILK) regulates integrin–extracellular matrix interactions and vascular integrity. This study investigated the role of ILK in CKD-associated vascular alterations. An adenine-supplemented diet induced a progressive CKD in wild-type (WT) and conditional ILK knock-down (cKD-ILK) mice. Aortic tissue was collected for histology and RT-qPCR analysis. Moreover, aortas were incubated ex vivo with the uremic toxins p-cresyl sulfate and indoxyl sulfate. In vitro, human aortic vascular smooth muscle cells were exposed to uremic toxins, and the effect of siRNA-mediated ILK silencing was tested. Aortas of adenine-fed WT mice showed a progressive increase in ILK expression, morphological alterations, and increased fibrosis, which was not observed in cKD-ILK aortas, compared to control mice. Statistically significant correlations between vascular content of ILK and fibrosis markers were observed. Ex vivo, uremic toxins increased ILK and fibrosis protein expression in WT aortas but not in cKD-ILK. In vitro, uremic toxins increased ILK activity and fibrosis markers, like collagen, while ILK-deleted cells prevented collagen increase. ILK depletion prevents CKD-associated vascular fibrosis, suggesting ILK as a potential therapeutic target to prevent arterial alterations in renal patients.