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Could a defective vasculature and aberrant VEGF...
Posted: Fri Feb 11, 2011 11:02 am
by gibbledygook
Could problems in VEGF (vascular endothelial growth factor) and therefore the vasculature be responsible for other neurodegenerative diseases?
Mol Neurobiol. 2011 Jan 28. [Epub ahead of print]
Evolution of the VEGF-Regulated Vascular Network from a Neural Guidance System.
Ponnambalam S, Alberghina M.
Endothelial Cell Biology Unit, Institute of Molecular & Cellular Biology, LIGHT Laboratories, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK,
s.ponnambalam@leeds.ac.uk.
Abstract
The vascular network is closely linked to the neural system, and an interdependence is displayed in healthy and in pathophysiological responses. How has close apposition of two such functionally different systems occurred? Here, we present a hypothesis for the evolution of the vascular network from an ancestral neural guidance system. Biological cornerstones of this hypothesis are the vascular endothelial growth factor (VEGF) protein family and cognate receptors. The primary sequences of such proteins are conserved from invertebrates, such as worms and flies that lack discernible vascular systems compared to mammals, but all these systems have sophisticated neuronal wiring involving such molecules. Ancestral VEGFs and receptors (VEGFRs) could have been used to develop and maintain the nervous system in primitive eukaryotes. During evolution, the demands of increased morphological complexity required systems for transporting molecules and cells, i.e., biological conductive tubes. We propose that the VEGF-VEGFR axis was subverted by evolution to mediate the formation of biological tubes necessary for transport of fluids, e.g., blood. Increasingly, there is evidence that aberrant VEGF-mediated responses are also linked to neuronal dysfunctions ranging from motor neuron disease, stroke, Parkinson's disease, Alzheimer's disease, ischemic brain disease, epilepsy, multiple sclerosis, and neuronal repair after injury, as well as common vascular diseases (e.g., retinal disease). Manipulation and correction of the VEGF response in different neural tissues could be an effective strategy to treat different neurological diseases.
PMID: 21271303 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21271303
Re: Could a defective vasculature and aberrant VEGF...
Posted: Tue Nov 08, 2011 10:05 am
by Billmeik
this same idea was just posited to me by a braniac relative and I found your post by googling.
vascular endothelial growth factor.
a good thing to check levels on if possible?
Re: Could a defective vasculature and aberrant VEGF...
Posted: Thu Nov 10, 2011 6:27 am
by gibbledygook
Hi, I'm not sure how easy it it to check VEGF levels but if you look in PubMed I think there are a few studies linking problems here and MS. I think the central problems remain mechanical with vertebral and venous compression causing back flow in cerebrospinal fluid and blood. But at the margin altering VEGF may help. I think!
Re: Could a defective vasculature and aberrant VEGF...
Posted: Thu Nov 10, 2011 7:55 am
by cheerleader
VEGF is a signaling protein that stimulates angiogenesis (creation of new blood vessels) and restores oxygen suppy to tissue when blood circulation in inadequte. VEGF levels in MS lesions is very high---which points to a connection of MS with the vasculature, as Gibbs states at the beginning....
http://www.ncbi.nlm.nih.gov/pubmed/12387457
Having high levels of VEGF indicates endothelial dysfunction and a break down in the BBB. You don't necessarily want to reduce VEGF levels, you want to reduce the situation that creates the body's need for higher VEGF levels.
In the CCSVI model, by opening venous malformations and allowing for better perfusion of the brain and spine, VEGF levels should normalize. But we don't typically do serum testing for VEGF levels. We test for inflammatory markers, like levels of C-reactive protein or SED/ESR rates. Jeff's serum number markers for inflammation have all normalized since venoplasty. They were off the charts high during his first MS flare.
cheer
Re: Could a defective vasculature and aberrant VEGF...
Posted: Fri Nov 11, 2011 11:13 am
by CindyCB
Cheer, just wondering if Jeff was and still is on anticoag therapy since his procedure?
Re: Could a defective vasculature and aberrant VEGF...
Posted: Fri Nov 11, 2011 11:49 am
by cheerleader
CindyCB wrote:Cheer, just wondering if Jeff was and still is on anticoag therapy since his procedure?
yes, Cindy- he is still on pradaxa, now nine months since last venoplasty. He's doing well on a lower dosage, and may remain on it for awhile longer. No restenosis, no new narrowings, he no longer hears the blood whooshing past his eardrum. No MS progression, new lesions or exacerbations. He's still mountain biking, eating well, taking supplements, feels great. I think longer anticoagulation therapy plus lifestyle changes may help keep restenosis at bay. We'll see!
cheer
Re: Could a defective vasculature and aberrant VEGF...
Posted: Fri Nov 11, 2011 11:57 am
by CindyCB
Interesting - really pleased to hear he's doing so well.
I wonder if Pradaxa has any anti-inflammatory properties to it, like aspirin does etc?
Did he ever get checked for Hughes/APS after his MS diagnosis?
Re: Could a defective vasculature and aberrant VEGF...
Posted: Fri Nov 11, 2011 2:42 pm
by cheerleader
Cindy--
Jeff was checked for everything, including Lyme by Igenex and Antiphospholid Syndrome (Hughes). Trust me, we went thru every single differential
He had hypercoagulation at his diagnosis, which is what started me searching into the vascular connection in '07 (here's a note I recently wrote about it on FB)
What's blood got to do with it?
https://www.facebook.com/note.php?note_ ... 5756162211
and lead to the Endothelial Health program.
http://www.ccsvi.org/index.php/helping- ... ial-health
His coagulation numbers have been good since starting the endo health program, but we're being extra careful after the 3rd procedure.
cheer
Re: Could a defective vasculature and aberrant VEGF...
Posted: Sat Nov 12, 2011 3:37 am
by CindyCB
Thanks for the links - very interesting!
I was kinda wondering if his continued success is in part helped out by the longer term Pradaxa. I've been taking 150mg aspirin (for daily headache/migraine) for about 8 months now and my ESR has finally dropped after steadily rising for a number of years.
I'm sure you know this already but you can test negative for Hughes/APS and still have it (sero-negative) and Prof. Hughes himself has linked it to MS.
http://qjmed.oxfordjournals.org/content ... 34fc0d5cf3