Expression of TGF-beta1 and beta3 but not apoptosis factors relates to flow-induced aortic enlargement.
BACKGROUND
Cell proliferation and apoptosis are both involved in arterial wall remodeling. Increase in blood flow induces arterial enlargement. The molecular basis of flow-induced remodeling in large elastic arteries is largely unknown.


METHODS
An aortocaval fistula (ACF) model in rats was used to induce enlargement in the abdominal aorta. Aortic gene expression of transforming growth factors beta (TGF-beta) and apoptosis-related factors was assessed at 1 and 3 days and 1, 2, 4, and 8 weeks. Expression levels were determined using a ribonuclease protection assay and western blotting. Cell proliferation and apoptosis were analyzed using BrdU incorporation and TUNEL techniques.


RESULTS
Blood flow increased 5-fold immediately after ACF (P<0.05). Lumen diameter of the aorta was 30% and 75% larger at 2 and 8 weeks respectively than those of controls (P<0.05). mRNA levels of TGF-beta1 and TGF-beta3 increased after ACF, peaked at 3 days (P<0.05) and returned to normal level at 1 week and thereafter. Western blotting showed enhanced expression of TGF-beta1 at 3 days and TGF-beta3 at 1 and 3 days and 1 week (P<0.05). mRNA levels of Bcl-xS initially decreased at 1 day, 3 days and 1 week, followed a return to baseline level at 2 weeks. Cell proliferation was observed at all time points after ACF (P<0.001 vs. controls) with proliferation in endothelial cells more significant than smooth muscle cells. Apoptosis was not significant.


CONCLUSIONS
Gene expression of TGF-beta1 and beta3 precedes arterial enlargement. Expression of apoptosis related factors is little regulated in the early stage of the flow-induced arterial remodeling.
Xu
Chengpei
C
Department of Surgery, Stanford University, Stanford, California, USA. cx11@stanford.edu
Lee
Sheila
S
Shu
Chang
C
Masuda
Hirotake
H
Zarins
Christopher K
CK
D000818:Animals; D001012:Aorta, Abdominal; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D018056:Hemorheology; D008297:Male; D023421:Models, Animal; D011167:Portacaval Shunt, Surgical / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; C508962:Tgfb1 protein, rat; C509046:Tgfb3 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D051020:bcl-X Protein