Structural and functional disruption of vascular smooth muscle cells in a transgenic mouse model of amyloid angiopathy.
The deposition of amyloid Abeta peptide in the wall of cerebral vessels (cerebral amyloid angiopathy), can lead to weakness and rupture of the vessel wall, resulting in hemorrhagic stroke. The Tg2576 transgenic mouse line, overexpressing mutant amyloid precursor protein in an age-dependent manner, forms amyloid angiopathy morphologically similar to that seen in the human. We report here the structural and functional disruption of smooth muscle cells (SMCs) in the walls of pial vessels affected by amyloid deposition in the Tg2576 mouse. We demonstrate, using multiphoton imaging, that the arrangement of SMCs becomes disorganized before the onset of cell death, and that these disorganized SMCs are unable to respond appropriately to application of endothelial-dependent and endothelial-independent vasodilators in a closed-cranial window preparation.
Department of Neurology, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129, USA.
R
R
Christie
M
M
Yamada
M
M
Moskowitz
B
B
Hyman
D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology* / Q000503:physiopathology*; D002550:Cerebral Veins / Q000187:drug effects / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D021621:Imaging, Three-Dimensional; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000503:physiopathology*; D009154:Mutation; D009599:Nitroprusside / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine