Monday, March 8, 2010
Vascular endothelial Growth factor is a fascinating molecule that has now entered the field of nephrology in the last decade. It's implications are very important in many diseases. Tight control of this molecule might be important for podocyte development and function as we are learning.
A nice resource and an article that everyone should read is linked above. In this paper, the authors show that glomerular-selective deletion or overexpression of VEGF-A leads to glomerular disease in mice. Podocyte-specific heterozygosity for VEGF-A resulted in renal disease within two weeks that looked like renal TMA and pre elampsia like. Homozygous deletion of VEGF-A in glomeruli resulted in premature death of the mice and finally overexpression of the VEGF-164 isoform led to a striking collapsing glomerulopathy, the lesion seen in HIV-associated nephropathy.
So basically to say it in simple terms: Too little VEGF or inhibition of VEGF leads to pre eclampsia like biopsy findings or thrombotic microangiopathy like findings( this has been shown independently in pre eclamptic patients as well and also in patients who are on chemotherapy agents that are anti VEGF agents:- bevacizumab,sunitinib, sorafinib and so forth)
Too much VEGF is noted in collapsing FSGS.
So there are two different spectrum of glomerular diseases that are seen with extremes of VEGF
( one with blood less glomeruli and the other with a collapsing glomeruli)
Very fascinating: Worth reviewing the Nephropathology of VEGF
Image source: biooncology.com
Other good references:
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