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Development of aneurysm‐like remodeling on vessels subjected to impinging flow
Author(s) -
Meng Hui,
Swartz D D,
Wang Z J,
Gao L,
Hoi Y,
Kolega J,
Metaxa E,
Szymanski M P,
Paciorek A M,
Yamamoto J,
Sauvageau E,
Levy E I,
Hopkins L N
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb116-b
Subject(s) - hemodynamics , intimal hyperplasia , internal elastic lamina , aneurysm , anatomy , shear stress , medicine , cardiology , artery , materials science , radiology , smooth muscle , composite material
Cerebral aneurysms are associated with hemodynamic stresses at vessel bifurcations, but little is known about how the hemodynamic microenvironment at such locations leads to vascular change. We hypothesize that impinging flow creates complex local hemodynamics that lead to remodeling of the wall and aneurysms occur when this remodeling goes awry. To uncover relationships between hemodynamics at bifurcations and specific vascular changes leading to aneurysms, Y‐bifurcations were created by anastomosis of carotid arteries in dogs. We determined detailed local hemodynamics through in vivo imaging and Computational Fluid Dynamics (CFD), then examined tissue responses by histology and immunostaining. CFD results were superimposed on the histology. This revealed large gradients of wall shear stress and development of an intimal pad at the flow impingement site. Adjacent to the impingement, shear stress was higher but gradients lower, and a groove, indicative of early aneurysm, formed in the vessel wall. The intimal pad showed extensive intimal hyperplasia at 2 weeks but matured at 2 months, with a thicker media and resemblance to a normal bifurcation apex. The groove was striking at 2 months, with a denuded endothelial layer, disrupted internal elastic lamina, and thinned media. Immunostaining showed decreased smooth muscle cell density and proliferation and decreased fibronectin in the groove, further indicating the groove may be an early aneurysm. This model system allows identification of hemodynamic parameters that are important for cerebral aneurysm development and exploration of vascular remodeling – healthy or pathological – in response to changing hemodynamics in a living system. Supported by NIH/NINDS (1K25 NS047242 ‐01) and NSF (BES‐0302389).