Multiple Mechanisms in Renal Artery Stenosis-Induced Renal Interstitial Fibrosis

2014 ◽  
Vol 128 (1-2) ◽  
pp. 57-66 ◽  
Author(s):  
Rui Cui ◽  
Xiao Chen ◽  
Lei Peng ◽  
Jing Ma ◽  
Dan Zhu ◽  
...  
Keyword(s):  
Renal Artery ◽  
Renal Artery Stenosis ◽  
Interstitial Fibrosis ◽  
Artery Stenosis ◽  
Renal Interstitial Fibrosis

scholarly journals Inhibition of p38 MAPK attenuates renal atrophy and fibrosis in a murine renal artery stenosis model

2013 ◽  
Vol 304 (7) ◽  
pp. F938-F947 ◽  
Author(s):  
Diping Wang ◽  
Gina M. Warner ◽  
Ping Yin ◽  
Bruce E. Knudsen ◽  
Jingfei Cheng ◽  
...  
Keyword(s):  
Renal Artery ◽  
Renal Artery Stenosis ◽  
P38 Mapk ◽  
Interstitial Fibrosis ◽  
Critical Role ◽  
Artery Stenosis ◽  
Renal Diseases ◽  
Matrix Deposition ◽  
Interstitial Inflammation

Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-β-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.

scholarly journals Persistent kidney dysfunction in swine renal artery stenosis correlates with outer cortical microvascular remodeling

2011 ◽  
Vol 300 (6) ◽  
pp. F1394-F1401 ◽  
Author(s):  
Alfonso Eirin ◽  
Xiang-Yang Zhu ◽  
Victor H. Urbieta-Caceres ◽  
Joseph P. Grande ◽  
Amir Lerman ◽  
...  
Keyword(s):  
Renal Artery ◽  
Renal Dysfunction ◽  
Renal Artery Stenosis ◽  
Interstitial Fibrosis ◽  
Ex Vivo ◽  
Kidney Injury ◽  
Artery Stenosis ◽  
Spatial Density ◽  
Tubulointerstitial Injury ◽  
Altered Expression

Percutaneous transluminal renal stenting (PTRS) does not consistently improve renal function in patients with atherosclerotic renovascular disease, but the mechanisms underlying irreversible kidney injury have not been fully elucidated. We hypothesized that renal dysfunction after PTRS is linked to ongoing renal microvascular (MV) remodeling. Pigs were studied after 10 wk of atherosclerosis and renal artery stenosis (ARAS), ARAS treated with PTRS 4 wk earlier, and normal controls ( n = 10 each). Renal blood flow (RBF) and glomerular filtration rate (GFR) were studied using multidetector computer tomography. Renal microvascular architecture (micro-CT), angiogenic activity, oxidative stress, and fibrosis were evaluated ex vivo. Four weeks after PTRS, blood pressure was normalized. However, GFR and RBF remained similarly decreased in untreated ARAS and ARAS+PTRS ( P < 0.05 vs. normal). MV rarefaction was unaltered after revascularization, and the spatial density of outer cortical microvessels correlated with residual GFR. Interstitial fibrosis and altered expression of proangiogenic and profibrotic factors persisted after PTRS. Tubulointerstitial injury in ARAS persisted 4 wk after mechanically successful PTRS, and vessel loss correlated with residual renal dysfunction. MV loss and fibrosis in swine ARAS might account for persistent renal dysfunction after PTRS and underscore the need to assess renal parenchymal disease before revascularization.

Regression of Left Ventricular Hypertrophy Following Stenting of Renal Artery Stenosis

2007 ◽  
Vol 14 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Thomas Zeller ◽  
Aljoscha Rastan ◽  
Uwe Schwarzwälder ◽  
Christian Müller ◽  
Ulrich Frank ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Renal Artery ◽  
Renal Artery Stenosis ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Artery Stenosis
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