Aortic wall cell proliferation via basic fibroblast growth factor gene transfer limits progression of experimental abdominal aortic aneurysm.
OBJECTIVE
Our previous study demonstrated that high flow conditions stimulated cell proliferation in the aortic wall in a rat model of abdominal aortic aneurysm (AAA), and we speculated that there is a possible relation between medial cell density and aortic wall integrity. In the present study we delivered the basic fibroblast growth factor (bFGF) gene to the aortic wall of a rat AAA model and evaluated the effects of growth factor-enhanced smooth muscle cell (SMC) proliferation on aneurysm progression.


METHODS
AAA was induced in rats by means of infusion of porcine pancreatic elastase. Immediately after elastase infusion the abdominal aorta was filled with an expression plasmid vector containing the bFGF gene (bFGF group) or LacZ gene (control group); then gene transfer to the aortic wall was carried out with an in vivo electroporation method. The animals were killed 7 days after treatment, and the aneurysm was measured. The numbers of SMCs, macrophages, and endothelial cells were counted with immunostaining, and cell replication was evaluated with bromodeoxyuridine (BrdU) staining.


RESULTS
Aneurysm diameter in the bFGF group was significantly smaller than that in the control group (4.6 +/- 0.3 mm vs 6.5 +/- 1.4 mm; P <.01). The numbers of medial SMCs and BrdU-incorporated cells in the bFGF group were significantly greater than those in the control group (SMC, 101 +/- 34 per high-power field [hpf] vs 80 +/- 31/hpf; P <.05, BrdU, 107 +/- 63/hpf vs 50 +/- 33/hpf; P <.05), whereas no difference was detected in the numbers of macrophages and endothelial cells between the 2 groups.


CONCLUSIONS
Delivery of bFGF to the aortic wall induced significant enhancement of medial SMC proliferation, without an increase in inflammatory infiltration, then successfully limited aneurysm enlargement. These findings suggest that increased medial cellularity inhibits aneurysm formation, which possibly offers a clue for developing a new strategy for treatment of AAAs.
Hoshina
Katsuyuki
K
Division of Vascular Regeneration, Graduate School of Medicine, The University of Tokyo, Japan.
Koyama
Hiroyuki
H
Miyata
Tetsuro
T
Shigematsu
Hiroshi
H
Takato
Tsuyoshi
T
Dalman
Ronald L
RL
Nagawa
Hirokazu
H
D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology*; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D002452:Cell Count; D002455:Cell Division; D004195:Disease Models, Animal; D018274:Electroporation; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D018014:Gene Transfer Techniques; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016222:Fibroblast Growth Factor 2