title: Hypertension and Estrogen Deficiency Augment Aneurysmal Remodeling in the Rabbit Circle of Willis in Response to Carotid Ligation.
abstract: Increased cerebral blood flow has been shown to induce pathological structural changes in the Circle of Willis (CoW) in experimental models. Previously, we reported flow-induced aneurysm-like remodeling in the CoW secondary to flow redistribution after bilateral common carotid artery (CCA) ligation in rabbits. In the current study, we tested the hypothesis that loading rabbits with biological risk factors for vascular disease would increase flow-induced aneurysmal remodeling in the CoW. In the same series as the previously-reported bilateral CCA-ligation-alone (n  = 6) and sham surgery (n = 3) groups, eight additional female rabbits (the experimental group in this study) were subjected to two risk factors for intracranial aneurysm (hypertension and estrogen deficiency) and then bilateral CCA ligation. Upon euthanasia at 6 months, vascular corrosion casts of the CoW were created and analyzed by scanning electron microscopy for morphological changes and aneurysmal damage. In rabbits with hypertension and estrogen deficiency, arterial caliber increased throughout the CoW, similar to rabbits with CCA ligation alone. However, aneurysmal remodeling (i.e., local bulging) in the CoW was significantly greater than in CCA-ligation-only rabbits and was more widespread, presenting in regions that did not show aneurysmal changes after CCA ligation alone. Furthermore, hypertension and estrogen deficiency caused greater increases in vessel length and tortuosity. These results suggest that hypertension and estrogen deficiency make the CoW more vulnerable to flow-induced aneurysmal remodeling and tortuosity. We propose they do so by lowering the tolerance of vascular tissue to hemodynamic forces caused by CCA ligation, thus lowering the threshold necessary to incite vascular damage.
authors.affiliation: Toshiba Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York.|Department of Biomedical Engineering, University at Buffalo, Buffalo, New York.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Tutino
authors.affiliation: Toshiba Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York.|Department of Mechanical and Aerospace Engineering, University at Buffalo, Buffalo, New York.
authors.forename: Max
authors.initials: M
authors.lastname: Mandelbaum
authors.affiliation: Department of Neuroendovascular Therapy, Tohoku University, Sendai, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Toshiba Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York.|Department of Neurosurgery, University at Buffalo, Buffalo, New York.
authors.forename: Liza C
authors.initials: LC
authors.lastname: Pope
authors.affiliation: Toshiba Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York.|Department of Neurosurgery, University at Buffalo, Buffalo, New York.|Department of Radiology, University at Buffalo, Buffalo, New York.
authors.forename: Adnan
authors.initials: A
authors.lastname: Siddiqui
authors.affiliation: Toshiba Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York.|Department of Pathology and Anatomical Sciences, University at Buffalo, Buffalo, New York.
authors.forename: John
authors.initials: J
authors.lastname: Kolega
authors.affiliation: Toshiba Stroke and Vascular Research Center, University at Buffalo, Buffalo, New York.|Department of Biomedical Engineering, University at Buffalo, Buffalo, New York.|Department of Mechanical and Aerospace Engineering, University at Buffalo, Buffalo, New York.|Department of Neurosurgery, University at Buffalo, Buffalo, New York.
authors.forename: Hui
authors.initials: H
authors.lastname: Meng
mesh_terms: D000818:Animals; D002340:Carotid Artery Diseases / Q000150:complications / Q000473:pathology*; D002560:Cerebrovascular Circulation; D002941:Circle of Willis / Q000473:pathology*; D004195:Disease Models, Animal; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D006973:Hypertension / Q000150:complications* / Q000473:pathology; D002532:Intracranial Aneurysm / Q000209:etiology / Q000473:pathology*; D008026:Ligation; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D012720:Severity of Illness Index
chemical_list: D004967:Estrogens
keywords: aneurysm initiation; aneurysm risk factors; arterial tortuosity; carotid artery ligation; de novo intracranial aneurysm