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Progression of renal fibrosis: the underestimated role of endothelial alterations.

Guerrot D, Dussaule JC, Kavvadas P, Boffa JJ, Chadjichristos CE, Chatziantoniou C - Fibrogenesis Tissue Repair (2012)

Bottom Line: The vasculature of the kidney is a heterogeneous structure, whose functional integrity is essential for the regulation of renal function.Although systemic endothelial dysfunction is undoubtedly associated with chronic kidney disease, the role of the renal endothelium in the initiation and the progression of renal fibrosis remains largely elusive.In this article, we critically review recent evidence supporting direct and indirect contributions of renal endothelial alterations to fibrosis in the kidney.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM U702, Tenon Hospital, Paris, France ; Université Pierre et Marie Curie, Paris, France ; Service de Néphrologie, CHU Hôpitaux de Rouen, Rouen, France.

ABSTRACT
The vasculature of the kidney is a heterogeneous structure, whose functional integrity is essential for the regulation of renal function. Owing to the importance of the endothelium in vascular biology, chronic endothelial alterations are therefore susceptible to impair multiple aspects of renal physiology and, in turn, to contribute to renal fibrosis. Although systemic endothelial dysfunction is undoubtedly associated with chronic kidney disease, the role of the renal endothelium in the initiation and the progression of renal fibrosis remains largely elusive. In this article, we critically review recent evidence supporting direct and indirect contributions of renal endothelial alterations to fibrosis in the kidney. Specifically, the potential implications of renal endothelial dysfunction and endothelial paucity in parenchymal hypoxia, in the regulation of local inflammation, and in the generation of renal mesenchymal cells are reviewed. We thereafter discuss therapeutic perspectives targeting renal endothelial alterations during the initiation and the progression of renal fibrogenesis.

No MeSH data available.


Related in: MedlinePlus

Schematic view of the pathophysiological role of endothelial activation in chronic kidney disease progression. (ADMA assymetrical dymethylarginine; ROS reactive oxygen species; AGE advanced glycation end products; TGF transforming growth factor; TNF tumor necrosis factor; IL interleukin; IFN interferon; EndMT endothelial-mesenchymal transition; Cx40 Connexin 40: Cx43 Connexin 43.)
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Figure 1: Schematic view of the pathophysiological role of endothelial activation in chronic kidney disease progression. (ADMA assymetrical dymethylarginine; ROS reactive oxygen species; AGE advanced glycation end products; TGF transforming growth factor; TNF tumor necrosis factor; IL interleukin; IFN interferon; EndMT endothelial-mesenchymal transition; Cx40 Connexin 40: Cx43 Connexin 43.)

Mentions: Although the recognition of a systemic endothelial disease related to CKD has led to significant research interest, fewer studies have specifically focused on endothelial alterations within the diseased kidney. We have shown that pharmacological NO deficiency led to ET-1 production in the injured renal endothelial cells with direct profibrotic consequences in the kidney [15]. Recent evidence provides novel insights on the pathophysiological role of intrarenal endothelium in the progression of CKD (Figure 1). In this review we analyze direct and indirect consequences of endothelial alterations on hemodynamics, inflammation and fibrogenesis in the kidney, and discuss therapeutic issues targeting this underestimated culprit in renal fibrosis.


Progression of renal fibrosis: the underestimated role of endothelial alterations.

Guerrot D, Dussaule JC, Kavvadas P, Boffa JJ, Chadjichristos CE, Chatziantoniou C - Fibrogenesis Tissue Repair (2012)

Schematic view of the pathophysiological role of endothelial activation in chronic kidney disease progression. (ADMA assymetrical dymethylarginine; ROS reactive oxygen species; AGE advanced glycation end products; TGF transforming growth factor; TNF tumor necrosis factor; IL interleukin; IFN interferon; EndMT endothelial-mesenchymal transition; Cx40 Connexin 40: Cx43 Connexin 43.)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368764&req=5

Figure 1: Schematic view of the pathophysiological role of endothelial activation in chronic kidney disease progression. (ADMA assymetrical dymethylarginine; ROS reactive oxygen species; AGE advanced glycation end products; TGF transforming growth factor; TNF tumor necrosis factor; IL interleukin; IFN interferon; EndMT endothelial-mesenchymal transition; Cx40 Connexin 40: Cx43 Connexin 43.)
Mentions: Although the recognition of a systemic endothelial disease related to CKD has led to significant research interest, fewer studies have specifically focused on endothelial alterations within the diseased kidney. We have shown that pharmacological NO deficiency led to ET-1 production in the injured renal endothelial cells with direct profibrotic consequences in the kidney [15]. Recent evidence provides novel insights on the pathophysiological role of intrarenal endothelium in the progression of CKD (Figure 1). In this review we analyze direct and indirect consequences of endothelial alterations on hemodynamics, inflammation and fibrogenesis in the kidney, and discuss therapeutic issues targeting this underestimated culprit in renal fibrosis.

Bottom Line: The vasculature of the kidney is a heterogeneous structure, whose functional integrity is essential for the regulation of renal function.Although systemic endothelial dysfunction is undoubtedly associated with chronic kidney disease, the role of the renal endothelium in the initiation and the progression of renal fibrosis remains largely elusive.In this article, we critically review recent evidence supporting direct and indirect contributions of renal endothelial alterations to fibrosis in the kidney.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM U702, Tenon Hospital, Paris, France ; Université Pierre et Marie Curie, Paris, France ; Service de Néphrologie, CHU Hôpitaux de Rouen, Rouen, France.

ABSTRACT
The vasculature of the kidney is a heterogeneous structure, whose functional integrity is essential for the regulation of renal function. Owing to the importance of the endothelium in vascular biology, chronic endothelial alterations are therefore susceptible to impair multiple aspects of renal physiology and, in turn, to contribute to renal fibrosis. Although systemic endothelial dysfunction is undoubtedly associated with chronic kidney disease, the role of the renal endothelium in the initiation and the progression of renal fibrosis remains largely elusive. In this article, we critically review recent evidence supporting direct and indirect contributions of renal endothelial alterations to fibrosis in the kidney. Specifically, the potential implications of renal endothelial dysfunction and endothelial paucity in parenchymal hypoxia, in the regulation of local inflammation, and in the generation of renal mesenchymal cells are reviewed. We thereafter discuss therapeutic perspectives targeting renal endothelial alterations during the initiation and the progression of renal fibrogenesis.

No MeSH data available.


Related in: MedlinePlus