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

Abstract

Purpose 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 imaging with magnetic resonance angiography (PC MRI/MRA). Material and methods In 23 pigs, the left renal artery was completely embolized using polyvinyl acrylide (PVA) particles and the right kidney partially embolized (remnant kidney) while six pigs served as controls. The animals were sacrificed 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). MRI/PC MRA of the kidneys was performed prior to sacrifice. The remnant and control kidneys were harvested for Western blotting of VEGF-A, MMP-1, and MIF. Blood was removed for BUN and creatinine prior to embolization and at time of sacrifice. 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 to 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<0.05 when compared to control). Masson's trichrome staining of the remnant kidney revealed 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.

Reproducibility of MRI renal artery blood flow and BOLD measurements in patients with chronic kidney disease and healthy controls

“…MRI has been used to determine renal artery blood flow (RABF). The method has been used in pigs subjected to the remnant kidney model , as well as in patients with CKD , infants with kidney transplants , and healthy subjects . However, MRI‐based RABF measurements are currently not used in clinical practise, partly because reproducibility is uncertain.…”

Blood Outgrowth Endothelial Cells Reduce Hypoxia-Mediated Fibroblast to Myofibroblast Conversion by Decreasing Proangiogenic Cytokines

“…Interestingly, each of these proteins has been found to be elevated and associated with VNH [9-13,25,26]. We determined the messenger RNA levels for each of these genes using RT-PCR and found that they were all reduced in fibroblast in contact with BOEC compared to fibroblasts alone.…”

Expression of Profibrotic Genes in a Murine Remnant Kidney Model

“…These include increased expression of proteins involved in inflammation, angiogenesis, and extracellular matrix deposition (13, 15, 33, 34). Matrix metalloproteinase (MMPs) are a family of extracellular matrix degrading proteinases.…”

“…There have been several studies, which have demonstrated involvement of VEGF-A in chronic kidney disease, diabetic nephropathy, glomerulosclerosis, and the remnant kidney model (15, 33, 34). Furthermore, inhibiting VEGF-A function using angiostatin has shown to decrease extracellular matrix deposition in the rat remnant kidney model (14).…”