High-flow-induced arterial remodeling in rats with different susceptibilities to cerebral aneurysms.
BACKGROUND
The higher incidence of cerebral aneurysms (CAs) induced by enhanced arterial blood flow in Long Evans (LE) compared to Brown Norway (BN) rats suggests that intrinsic differences in high-flow arterial remodeling may be involved in determining CA susceptibility. Some aspects of this remodeling were compared in LE and BN rats after creation of an abdominal aortocaval fistula (ACF).


RESULTS
At 4 days with ACF, aortic luminal cross-sectional area (LCSA) determined by morphometry was increased by 20% in LE but not in BN rats. mRNA levels, determined by RT-PCR, were higher in LE than in BN rats for collagen alpha1(I), collagen alpha1(III), MMP2 and its inhibitor TIMP1 at 19 days with ACF. Nitric oxide synthase (NOS) mRNA levels were higher in LE rats at 4 days for the inducible (NOS2) isoform and at 4 and 19 days for the neuronal (NOS1) isoform. Aortic LCSA and NOS1 mRNA levels were tightly correlated and NOS inhibition prevented ACF-induced aortic remodeling in the LE rat. MMP2 and MMP7 activity, evaluated by zymography at 4 days with ACF, did not greatly differ between BN and LE.


CONCLUSIONS
These data suggest that a higher intrinsic ability for high-flow-induced arterial enlargement associated with NOS gene overexpression may be a possible genetic determinant in CA susceptibility.
Coutard
Michèle
M
INSERM U698, Hôpital Xavier Bichat, Paris, France. coutard@bichat.inserm.fr
Osborne-Pellegrin
Mary
M
Fontaine
Vincent
V
Jacob
Marie-Paule
MP
Michel
Jean-Baptiste
JB
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D001018:Aortic Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D001166:Arteriovenous Shunt, Surgical; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000209:etiology* / Q000235:genetics; D008297:Male; D045726:Metalloproteases / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012039:Regional Blood Flow; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014684:Venae Cavae / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019001:Nitric Oxide Synthase; D045726:Metalloproteases