FUNCTIONAL ANALYSIS OF VON WILLEBRAND FACTOR IN MOUSE MODEL OF ACUTE ISCHEMIA-REPERFUSION KIDNEY INJURY
(Abstract release date: 05/19/16)
EHA Library. Sugimoto M. 06/09/16; 133100; E1551
Dr. Mitsuhiko Sugimoto
Contributions
Contributions
Abstract
Abstract: E1551
Type: Eposter Presentation
Background
Acute kidney injury (AKI), an abrupt loss of renal function, is often seen in clinical settings and may become fatal. The adhesive protein von Willebrand factor (VWF) plays a pivotal role in platelet thrombus formation under high shear stress conditions and is recently understood as a key protein in a cross-talk between inflammation and thrombosis.
Aims
We therefore assumed that VWF may be involved in the pathophysiology of AKI, the major cause of which could be an insufficient renal circulation and/or inflammatory cell infiltration in the kidney. To test this hypothesis, we studied the relevant role of VWF in AKI in mouse model of acute ischemia-reperfusion (I/R) kidney injury.
Methods
Mice (male, 8-12 weeks of age), whose right kidney were surgically removed 1 week prior to the kidney I/R experiment, were anesthetized with inhaled isoflurane and then placed in an abdominal position on a heating pad. Surgical incision was given on the left side of back and the left kidney was brought out and kept outside during the operation. Both renal artery and vein were clamped at the renal hilus by a clamping clip for 30 min ischemia. Then a clip was taken off to provoke the reperfusion of renal blood flow, which was monitored by Laser Doppler flowmetry. The kidney was then put back in a body and skin incision was closed. The renal blood flow was measured again 30 h after reperfusion and mice were then sacrificed for blood collection.
Results
We compared 15 wild-type (WT) and 16 VWF-gene deleted (knock-out; KO) mice (from The Jackson Laboratory, Bar Harbor, ME). Excess blood loss was not observed in all mice (WT or KO) during whole surgical process. Although no difference was seen immediately after reperfusion, significantly (p < 0.05) higher renal blood flow at 30 h after reperfusion was confirmed in VWF-KO mice, as compared to WT (KO; 24.0±2.3 vs. WT; 15.1±1.46 ml/min/100g of kidney weight, and the reperfusion/base flow ratio: KO; 1.0±0.07 vs. WT; 0.6 ±0.07). Consistent with the renal blood flow data, the serum creatinine value at 30 h after reperfusion were significantly (p < 0.05) lower in VWF-KO mice than WT (KO; 2.77±0.11 vs. WT; 3.15±0.11 mg/dl).
Conclusion
Our results suggest that VWF does play a role in the pathogenesis of AKI, in which VWF-dependent thrombotic or inflammatory responses may trigger thrombotic ischemia or endothelial damages of vascular bed in the kidney. Thus, proper functional regulation of VWF would be beneficial for better microcirculation and vessel functions in the kidney, suggesting a novel therapeutic potential against AKI.
Session topic: E-poster
Keyword(s): Acute renal failure, Knockout mice, VWF
Type: Eposter Presentation
Background
Acute kidney injury (AKI), an abrupt loss of renal function, is often seen in clinical settings and may become fatal. The adhesive protein von Willebrand factor (VWF) plays a pivotal role in platelet thrombus formation under high shear stress conditions and is recently understood as a key protein in a cross-talk between inflammation and thrombosis.
Aims
We therefore assumed that VWF may be involved in the pathophysiology of AKI, the major cause of which could be an insufficient renal circulation and/or inflammatory cell infiltration in the kidney. To test this hypothesis, we studied the relevant role of VWF in AKI in mouse model of acute ischemia-reperfusion (I/R) kidney injury.
Methods
Mice (male, 8-12 weeks of age), whose right kidney were surgically removed 1 week prior to the kidney I/R experiment, were anesthetized with inhaled isoflurane and then placed in an abdominal position on a heating pad. Surgical incision was given on the left side of back and the left kidney was brought out and kept outside during the operation. Both renal artery and vein were clamped at the renal hilus by a clamping clip for 30 min ischemia. Then a clip was taken off to provoke the reperfusion of renal blood flow, which was monitored by Laser Doppler flowmetry. The kidney was then put back in a body and skin incision was closed. The renal blood flow was measured again 30 h after reperfusion and mice were then sacrificed for blood collection.
Results
We compared 15 wild-type (WT) and 16 VWF-gene deleted (knock-out; KO) mice (from The Jackson Laboratory, Bar Harbor, ME). Excess blood loss was not observed in all mice (WT or KO) during whole surgical process. Although no difference was seen immediately after reperfusion, significantly (p < 0.05) higher renal blood flow at 30 h after reperfusion was confirmed in VWF-KO mice, as compared to WT (KO; 24.0±2.3 vs. WT; 15.1±1.46 ml/min/100g of kidney weight, and the reperfusion/base flow ratio: KO; 1.0±0.07 vs. WT; 0.6 ±0.07). Consistent with the renal blood flow data, the serum creatinine value at 30 h after reperfusion were significantly (p < 0.05) lower in VWF-KO mice than WT (KO; 2.77±0.11 vs. WT; 3.15±0.11 mg/dl).
Conclusion
Our results suggest that VWF does play a role in the pathogenesis of AKI, in which VWF-dependent thrombotic or inflammatory responses may trigger thrombotic ischemia or endothelial damages of vascular bed in the kidney. Thus, proper functional regulation of VWF would be beneficial for better microcirculation and vessel functions in the kidney, suggesting a novel therapeutic potential against AKI.
Session topic: E-poster
Keyword(s): Acute renal failure, Knockout mice, VWF
Abstract: E1551
Type: Eposter Presentation
Background
Acute kidney injury (AKI), an abrupt loss of renal function, is often seen in clinical settings and may become fatal. The adhesive protein von Willebrand factor (VWF) plays a pivotal role in platelet thrombus formation under high shear stress conditions and is recently understood as a key protein in a cross-talk between inflammation and thrombosis.
Aims
We therefore assumed that VWF may be involved in the pathophysiology of AKI, the major cause of which could be an insufficient renal circulation and/or inflammatory cell infiltration in the kidney. To test this hypothesis, we studied the relevant role of VWF in AKI in mouse model of acute ischemia-reperfusion (I/R) kidney injury.
Methods
Mice (male, 8-12 weeks of age), whose right kidney were surgically removed 1 week prior to the kidney I/R experiment, were anesthetized with inhaled isoflurane and then placed in an abdominal position on a heating pad. Surgical incision was given on the left side of back and the left kidney was brought out and kept outside during the operation. Both renal artery and vein were clamped at the renal hilus by a clamping clip for 30 min ischemia. Then a clip was taken off to provoke the reperfusion of renal blood flow, which was monitored by Laser Doppler flowmetry. The kidney was then put back in a body and skin incision was closed. The renal blood flow was measured again 30 h after reperfusion and mice were then sacrificed for blood collection.
Results
We compared 15 wild-type (WT) and 16 VWF-gene deleted (knock-out; KO) mice (from The Jackson Laboratory, Bar Harbor, ME). Excess blood loss was not observed in all mice (WT or KO) during whole surgical process. Although no difference was seen immediately after reperfusion, significantly (p < 0.05) higher renal blood flow at 30 h after reperfusion was confirmed in VWF-KO mice, as compared to WT (KO; 24.0±2.3 vs. WT; 15.1±1.46 ml/min/100g of kidney weight, and the reperfusion/base flow ratio: KO; 1.0±0.07 vs. WT; 0.6 ±0.07). Consistent with the renal blood flow data, the serum creatinine value at 30 h after reperfusion were significantly (p < 0.05) lower in VWF-KO mice than WT (KO; 2.77±0.11 vs. WT; 3.15±0.11 mg/dl).
Conclusion
Our results suggest that VWF does play a role in the pathogenesis of AKI, in which VWF-dependent thrombotic or inflammatory responses may trigger thrombotic ischemia or endothelial damages of vascular bed in the kidney. Thus, proper functional regulation of VWF would be beneficial for better microcirculation and vessel functions in the kidney, suggesting a novel therapeutic potential against AKI.
Session topic: E-poster
Keyword(s): Acute renal failure, Knockout mice, VWF
Type: Eposter Presentation
Background
Acute kidney injury (AKI), an abrupt loss of renal function, is often seen in clinical settings and may become fatal. The adhesive protein von Willebrand factor (VWF) plays a pivotal role in platelet thrombus formation under high shear stress conditions and is recently understood as a key protein in a cross-talk between inflammation and thrombosis.
Aims
We therefore assumed that VWF may be involved in the pathophysiology of AKI, the major cause of which could be an insufficient renal circulation and/or inflammatory cell infiltration in the kidney. To test this hypothesis, we studied the relevant role of VWF in AKI in mouse model of acute ischemia-reperfusion (I/R) kidney injury.
Methods
Mice (male, 8-12 weeks of age), whose right kidney were surgically removed 1 week prior to the kidney I/R experiment, were anesthetized with inhaled isoflurane and then placed in an abdominal position on a heating pad. Surgical incision was given on the left side of back and the left kidney was brought out and kept outside during the operation. Both renal artery and vein were clamped at the renal hilus by a clamping clip for 30 min ischemia. Then a clip was taken off to provoke the reperfusion of renal blood flow, which was monitored by Laser Doppler flowmetry. The kidney was then put back in a body and skin incision was closed. The renal blood flow was measured again 30 h after reperfusion and mice were then sacrificed for blood collection.
Results
We compared 15 wild-type (WT) and 16 VWF-gene deleted (knock-out; KO) mice (from The Jackson Laboratory, Bar Harbor, ME). Excess blood loss was not observed in all mice (WT or KO) during whole surgical process. Although no difference was seen immediately after reperfusion, significantly (p < 0.05) higher renal blood flow at 30 h after reperfusion was confirmed in VWF-KO mice, as compared to WT (KO; 24.0±2.3 vs. WT; 15.1±1.46 ml/min/100g of kidney weight, and the reperfusion/base flow ratio: KO; 1.0±0.07 vs. WT; 0.6 ±0.07). Consistent with the renal blood flow data, the serum creatinine value at 30 h after reperfusion were significantly (p < 0.05) lower in VWF-KO mice than WT (KO; 2.77±0.11 vs. WT; 3.15±0.11 mg/dl).
Conclusion
Our results suggest that VWF does play a role in the pathogenesis of AKI, in which VWF-dependent thrombotic or inflammatory responses may trigger thrombotic ischemia or endothelial damages of vascular bed in the kidney. Thus, proper functional regulation of VWF would be beneficial for better microcirculation and vessel functions in the kidney, suggesting a novel therapeutic potential against AKI.
Session topic: E-poster
Keyword(s): Acute renal failure, Knockout mice, VWF
{{ help_message }}
{{filter}}