Vascular endothelial growth factor-A, matrix metalloproteinase-1, and macrophage migration inhibition factor changes in the porcine remnant kidney model: evaluation by magnetic resonance imaging.
OBJECTIVE
To determine the expression of vascular endothelial growth factor-A (VEGF-A), macrophage migration inhibition factor (MIF), and matrix metalloproteinase-1 (MMP-1) in the porcine remnant kidney model and quantify renal blood flow and volume using phase contrast magnetic resonance (PC MR) imaging with MR angiography.


METHODS
In 23 pigs, the left renal artery was completely embolized using polyvinyl acrylide (PVA) particles and the right kidney partially embolized (remnant kidney), and six pigs served as controls. The animals were killed early (day 3, 7, and 14, N=3), day 24 (D24, N=5), day 37 (D37, N=3), day 42 (D42, N=9), and day 84 (D84, N=3). MR imaging/PC MR angiography of the kidneys was performed before death. The remnant and control kidneys were harvested for Western blotting of VEGF-A, MMP-1, and MIF. Blood was removed for blood urea nitrogen (BUN) and creatinine before embolization and at time of death.


RESULTS
The kidney function after the embolization was characterized by chronic renal insufficiency. The renal artery blood flow, volume, and weight of the remnant kidney increased significantly over time when compared with controls. At early time points, there was increased expression of MIF and MMP-1 followed by an increase in the expression of VEGF-A by day 37 (P<.05 when compared with control). Masson's trichrome staining of the remnant kidney showed scarring in the tubulointerstitial space.


CONCLUSIONS
In this model, renal blood flow and volume increase as the remnant kidney hypertrophies and scars. There is increased expression of MIF, VEGF-A, and MMP-1 in the remnant kidney.
Misra
Sanjay
S
Department of Radiology, Mayo Clinic, Mayo Clinic, 200 First Street SW, Vascular and Interventional Radiology Translational Laboratory, Rochester, MN 55905, USA. misra.sanjay@mayo.edu
Misra
Khamal D
KD
Glockner
James F
JF
D000818:Animals; D002630:Chemotactic Factors / Q000378:metabolism*; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D002630:Chemotactic Factors; D042461:Vascular Endothelial Growth Factor A; C053609:macrophage migration enhancement factor; D020781:Matrix Metalloproteinase 1