Title
Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model
Author
TNO Kwaliteit van Leven
Hassane, S.
Claij, N.
Lantinga-van Leeuwen, I.S.
van Munsteren, J.C.
van Lent, N.
Hanemaaijer, R.
Breuning, M.H.
Peters, D.J.M.
de Ruiter, M.C.
Publication year
2007
Abstract
OBJECTIVE - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multi-system disorder characterized by progressive cyst formation in the kidneys. Serious complications of ADPKD are intracranial and aortic aneurysms. The condition is mainly caused by mutations in the PKD1 or PKD2 gene. We have carefully analyzed vascular remodeling in hypomorphic Pkd1 mouse model with dissecting aneurysms in the aorta. METHODS AND RESULTS - Quantitative real-time polymerase chain reaction revealed that in the aorta the expression of normal Pkd1 is reduced to approximately 26%. Using (immuno)histochemistry we have characterized the pathogenetic sequence for dissecting aneurysm formation. The aorta shows regions with accumulation of matrix components between the elastin lamellae. This is followed by increased numbers of smooth muscle cells and locally weakening of the media. In the intima, accumulation of matrix components and detachment of endothelial cells from the elastin lamellae results in a tear. The combination of weak media and a tear in the intima leads to rupture of the vessel wall resulting in intramural bleeding. CONCLUSIONS - The Pkd1 mouse reveals that polycystin1 is implicated in maintenance of the vessel wall structural integrity, and it is a useful model for dissecting aneurysm formation studies. © 2007 American Heart Association, Inc. Chemicals / CAS: calcium, 7440-70-2; collagen, 9007-34-5; elastin, 9007-58-3; fibronectin, 86088-83-7; gelatinase A, 146480-35-5; gelatinase B, 146480-36-6; osteopontin, 106441-73-0; perlecan, 143972-95-6; versican, 126968-45-4; polycystic kidney disease 1 protein; RNA, Messenger; TRPP Cation Channels
Subject
Biomedical Research
Aorta
Dissecting aneurysm
Extracellular matrix
Pkd1
Polycystic kidney disease
Aneurysm, Dissecting
Animals
Aorta
Aortic Aneurysm
Disease Models, Animal
Disease Progression
Endothelial Cells
Extracellular Matrix
Genotype
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation
Myocytes, Smooth Muscle
Phenotype
Polycystic Kidney Diseases
RNA, Messenger
Severity of Illness Index
TRPP Cation Channels
Tunica Intima
Tunica Media
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http://resolver.tudelft.nl/uuid:ebbf580f-98f2-4e94-ae91-b8a1859bbe11
DOI
https://doi.org/10.1161/atvbaha.107.149252
TNO identifier
240223
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 27 (27), 2177-2183
Document type
article