Intravascular radiation accelerates atherosclerotic lesion formation of hypercholesteremic rabbits.
OBJECTIVE
The purpose of the present study is to evaluate the effect of intravascular radiation (IR) on the arterial wall of uninjured vessels in the hypercholesteremic rabbit model.


METHODS
Aortas of 24 New Zealand white rabbits were treated with either intravascular 192-Ir gamma-radiation (15 Gy at 2 mm from the center of the source) or were exposed to the source catheter without radiation (sham controls). Following the radiation treatment, the animals were fed a 2% cholesterol diet until euthanasia at 2 (n=8) or 6 (n=16) weeks. Arteries were analyzed using light and scanning electron microscopy (SEM); transforming growth factor beta (TGF-beta) 1, a promoter of connective tissue deposition, was also monitored.


RESULTS
At 2 weeks, SEM analysis showed well-aligned endothelial cells in nonradiated segments, whereas irradiated arteries consistently contained adherent and subendothelial macrophages with focal areas of endothelial disruption. Further radiated segments at 2 weeks showed a 7-fold increase in active TGF beta-1 over nonradiated segments. At 6 weeks, there was a significant increase in plaque and vessel wall area relative to control arteries, however, no differences were noted in the density of actin-positive smooth muscle cells (SMCs) or macrophages. Similarly, no differences were noted in cell proliferation between groups as evidenced by the marker bromodeoxyuridine (BrdU). In contrast, nonirradiated segments frequently contained cellular areas with extracellular lipid.


CONCLUSIONS
Exposure of previously uninjured vessels to IR and hypercholesterolemia is associated with increased plaque burden and leads to more advanced plaque types. Special care should be taken to minimize radiation exposure in normal vascular segments in hypercholesterolemic patients undergoing radiation therapy.
Cottin
Y
Y
Medstar Research Institute, Washington Hospital Center, Washington, DC 20010, USA.
Kollum
M
M
Kolodgie
F D
FD
Chan
R C
RC
Kim
H S
HS
Vodovotz
Y
Y
Virmani
R
R
Waksman
R
R
Yazdi
H
H
D000818:Animals; D001011:Aorta / Q000528:radiation effects*; D001161:Arteriosclerosis / Q000209:etiology*; D001918:Brachytherapy; D005260:Female; D006937:Hypercholesterolemia / Q000150:complications / Q000473:pathology*; D007496:Iridium Radioisotopes; D008297:Male; D008855:Microscopy, Electron, Scanning; D011817:Rabbits; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis
D007496:Iridium Radioisotopes; D016212:Transforming Growth Factor beta