A case of acute renal injury and renal artery stenosis caused by cholesterol crystal embolization after coronary stenting: Improved by a combination therapy

Recent studies have shown that inflammation plays a critical role in the initiation and progression of hypertensive kidney disease, including renal artery stenosis. However, the signaling mechanisms underlying the induction of inflammation are poorly understood. We found that CXCL16 was induced in the kidney in a murine model of renal artery stenosis. To determine whether CXCL16 is involved in renal injury and fibrosis, wild-type and CXCL16 knockout mice were subjected to renal artery stenosis induced by placing a cuff on the left renal artery. Wild-type and CXCL16 knockout mice had comparable blood pressure at baseline. Renal artery stenosis caused an increase in blood pressure that was similar between wild-type and CXCL16 knockout mice. CXCL16 knockout mice were protected from RAS-induced renal injury and fibrosis. CXCL16 deficiency suppressed bone marrow-derived fibroblast accumulation and myofibroblast formation in the stenotic kidneys, which was associated with less expression of extracellular matrix proteins. Furthermore, CXCL16 deficiency inhibited infiltration of F4/80+ macrophages and CD3+ T cells in the stenotic kidneys compared with those of wild-type mice. Taken together, our results indicate that CXCL16 plays a pivotal role in the pathogenesis of renal artery stenosis-induced renal injury and fibrosis through regulation of bone marrow-derived fibroblast accumulation and macrophage and T-cell infiltration.

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Genetic Deficiency of T‐bet Protects Against Chronic Renal Injury in Murine Renal Artery Stenosis

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.802.68 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Mazen Osman ◽

Adam Osman ◽

Sonu Kashyap ◽

Hula Taha ◽

Karen Lien ◽

...

Keyword(s):

Renal Artery ◽

Renal Artery Stenosis ◽

Renal Injury ◽

Artery Stenosis ◽

Genetic Deficiency

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P0146MESENCHYMAL STEM CELLS AND THEIR EXTRACELLULAR VESICLES PROGENY DECREASE RENAL INJURY IN EXPERIMENTAL SWINE RENAL ARTERY STENOSIS THROUGH DIFFERENT MECHANISMS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0146 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Yu Zhao ◽

Xiao liang Zhang ◽

Bicheng Liu ◽

Lilach Lerman

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Renal Artery ◽

Renal Artery Stenosis ◽

Kidney Function ◽

Extracellular Vesicles ◽

Renal Injury ◽

Tissue Injury ◽

Ex Vivo ◽

Artery Stenosis

Abstract Background and Aims Novel therapies are needed to address the increasing prevalence of chronic kidney disease. Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) augment tissue repair. EVs have practical benefits, but their efficacy relative to MSCs is incompletely understood. We tested the hypothesis that EVs are as effective as MSCs in protecting the stenotic kidney but target different injury pathways. Method Pigs were studied after 16 weeks of renal injury achieved by diet-induced metabolic syndrome (Mets) and renal artery stenosis (RAS). Pigs were untreated or treated four weeks earlier with a single intrarenal delivery of autologous adipose tissue-derived MSCs (1 × 107) or EVs (1 × 1010). Lean pigs and sham RAS served as controls (n=6 each). Stenotic kidney function was studied in-vivo using CT. Histopathology and expression of necroptosis markers (RIPK-1 and RIPK-3), inflammatory and growth factors (angiopoeitin-1 and VEGF) was studied ex-vivo. Results Stenotic-kidney glomerular filtration rate and blood flow in Mets+RAS were both lower than Mets, increased in Mets+RAS+MSCs, and further improved in Mets+RAS+EV. Both MSCs and EVs improved renal function, hypoxia, and decreased renal fibrosis and apoptosis. MSC were slightly more effective in preserving microvascular density (0.02-0.2mm in diameter), and prominently attenuated renal inflammation. However, EVs more significantly upregulated growth-factor expression and decreased necropotosis. Conclusion: Adipose tissue-derived MSCs and their EVs both improve stenotic kidney function and decrease tissue injury in Mets+RAS. MSCs more effectively preserve the microcirculation, while EVs bestow better preservation of renal cellular integrity. These findings encourage further exploration of this novel approach to attenuate renal injury.

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