Angiogenesis in multiplesclerosis: is it good, bad or an epiphenomenon?
Joseph A. Frankb,
Stephen Karlikhttp://www.sciencedirect.com/science/ar ... 0X03003368
Fig. 1. Potential role for angiogenesis in MS. (1) Initially immune cells bind to the BBB through a variety of cell adhesion molecules. (2) Cells infiltrate the perivascular space. (3) Cytokine, immune and antibody mediated attack on the myelin in the perivascular space. (4) Infiltration of immune cells into the parenchyma. (5) Release of inflammatory and hypoxic mediators including VEGF, HIF-1, NO, ET-1 from various cell types. (6) Angiogenic signals cause the initiation of the formation of new blood vessels into the lesion area.http://journals.lww.com/jneuropath/Abst ... _in.9.aspx
Vascular Endothelial Growth Factor Is Expressed in Multiple Sclerosis Plaques and Can Induce Inflammatory Lesions in Experimental Allergic Encephalomyelitis Rats
PROESCHOLDT, MARTIN A. MD; JACOBSON, STEVEN PHD; TRESSER, NANCY MD; OLDFIELD, EDWARD H. MD; MERRILL, MARSHA J. PHD
The active lesions in multiple sclerosis (MS) are characterized by blood-brain-barrier (BBB) breakdown, upregulation of adhesion molecules on capillary endothelial cells, and perivascular inflammation, suggesting that altered vessel permeability and activated endothelial cells are involved in the pathogenesis of the disease. Vascular endothelial growth factor (VEGF) mediates multiple aspects of blood vessel physiology, including regulation of growth, permeability, and inflammation. To investigate a possible relationship between VEGF expression and CNS autoimmune disease, we examined VEGF expression in MS plaques compared to normal white matter by immunohistochemistry and in situ hybridization. VEGF expression was consistently upregulated in both acute and chronic MS plaques. We also examined VEGF expression during the course of experimental allergic encephalomyelitis (EAE) in rats. VEGF-positive cells with astrocytic morphology increased in the spinal cord during the development of EAE and were found in association with inflammatory cells. Furthermore, intracerebral infusion of VEGF in animals previously immunized with myelin basic protein induced an inflammatory response in the brain, whereas infusion of vehicle, or infusion of VEGF in naive animals, did not. These results suggest that overexpression of VEGF may exacerbate the inflammatory response in autoimmune diseases of the CNS by inducing focal BBB breakdown and migration of inflammatory cells into the lesions.
And another Yan Chang Patent claiming MCP controls angiogenesishttp://patft1.uspto.gov/netacgi/nph-Par ... PN/6890906
The present invention recognizes the role of galectins in angiogenesis, and provides a therapeutic material which will advantageously interact with galectins so as to moderate or prevent the manifestations of angiogenesis-dependent disease. Specifically, the present invention recognizes that particular carbohydrate materials will bind to or otherwise interact with galectins and thereby modify their interaction with cellular structures, and thereby control angiogenesis.
Galectins comprise a family of proteins which are expressed by plant and animal cells, and which bind .beta.-galactoside sugars. These proteins can be found on cell surfaces, in cytoplasm, and in extracellular fluids. They have a molecular weight in the general range of 29-34 kd; they have an affinity for .beta.-galactoside containing materials, and have been found to play important roles in a number of biological processes. Galectin-1 and galectin-3 are specific members of this family which have been found to interact with various cellular structures, and galectin-3 has been demonstrated to promote angiogenesis in vitro.
Yadda yadda yadda including a chart (more legible in google patents) showing lab results of the impact of MCP on VEGF levels (it decreased VEGF significantly)