Angiogenic proteins are expressed by brain blood vessels in Alzheimer's disease.
Data are emerging to support the idea that mediators of angiogenesis are found in the Alzheimer's disease (AD) brain. The objective of this study is to compare the expression of the angiogenic mediators vascular endothelial growth factor (VEGF), angiopoietin, and matrix metalloproteinases (MMPs) in the microcirculation of AD patients and age-matched controls. Our results indicate that angiopoietin-2 and VEGF are expressed by AD- but not control-derived microvessels. AD-derived microvessels also release higher levels of MMP-2 and MMP-9 compared to controls. The data show that despite high levels of MMP-9, assessed by western blot, MMP-9 activity is not detectable in AD microvessels. In this regard we find high levels of the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in AD, but not control vessels. Furthermore, we explore the ability of thrombin, previously shown to be present in AD microvessels, to affect TIMP expression in cultured brain endothelial cells and find that thrombin causes up regulation of TIMP-1. These data show that angiogenic changes occur in the microcirculation of the AD brain and suggest that if these changes are contributory to disease pathogenesis, targeting the abnormal brain endothelial cell would provide a novel therapeutic approach for the treatment of this disease.
Thirumangalakudi
Lakshmi
L
Garrison Institute on Aging and Department of Neuropsychiatry and Behavioral Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Samany
Pezhman Ghatreh
PG
Owoso
Akinkunle
A
Wiskar
Brandt
B
Grammas
Paula
P
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008833:Microcirculation / Q000502:physiology; D016133:Polymerase Chain Reaction; D051381:Rats; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D042501:Angiogenic Proteins; D018076:DNA, Complementary; D019714:Tissue Inhibitor of Metalloproteinases; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases