Impaired angiogenesis in a transgenic mouse model of cerebral amyloidosis.
Abeta peptides are naturally occurring peptides, which are thought to play a key role in the pathophysiology of Alzheimer's disease (AD). In AD cases, levels of soluble and insoluble Abeta peptides increase in the brain as well as in the cerebrovasculature, a phenomenon that does not occur in extra-cranial vessels. There are frequently anomalies in the cerebrovasculature in AD, and despite increases in several pro-angiogenic factors in AD brain, evidence for increased vascularity is lacking; in fact there is evidence to the contrary. It has also been recently shown that Abeta peptides may have profound anti-angiogenic effects in vitro and in vivo. We therefore investigated whether there is evidence for altered angiogenesis in the vasculature in a transgenic mouse model of Abeta amyloidosis (Tg APPsw line 2576). In vitro, the formation of capillary-like structures on a reconstituted extracellular matrix by endothelial cells isolated from Tg APPsw is impaired. Ex vivo, the sprouting of new capillaries from arterial explants (over expressing Abeta) isolated from 9-month-old Tg APPsw is reduced compared to arterial explants isolated from control littermates. In addition, Tg APPsw mice show a reduction in vascular density in the cortex and hippocampus compared to control littermates. Altogether, our data suggest that the over expression of APPsw in the vasculature may oppose angiogenesis.
Paris
Daniel
D
The Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA. dparis@rdfn.org
Patel
Nikunj
N
DelleDonne
Anthony
A
Quadros
Amita
A
Smeed
Robert
R
Mullan
Michael
M
D000375:Aging / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000098:blood supply; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000473:pathology; D006624:Hippocampus / Q000098:blood supply; D066298:In Vitro Techniques; D007797:Laminin; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011509:Proteoglycans; D014684:Venae Cavae / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen