Delayed re-endothelialization and T-cell infiltration following intracoronary radiation therapy in the porcine model.
OBJECTIVE
To evaluate the late induction of apoptosis following intracoronary radiation (IR) and the effects of IR on inflammatory cells.


METHODS
Porcine coronaries were injured by balloon overstretch followed by either 0 or 15 Gy of 192Ir prescribed to 2 mm from the center of the source. Swine were euthanized at 3, 7, and 14 days posttreatment, and arteries were stained for markers of smooth muscle cells (SMCs alpha-actin), T cells (CD3), macrophages, endothelial cells, and apoptotic nuclei (terminal uridine nick end labeling, TUNEL). Intimal area (IA) and IA corrected for medial fracture length (IA/FL) were quantified by digital image analysis, which was also used to quantify the distribution of immunostain-positive cells in the adventitia, media, and neointima, respectively.


RESULTS
IA/FL was significantly reduced following treatment with 15 Gy, in association with decreased SMC density. Following injury and IR, TUNEL- and CD3-positive cell density increased significantly, and density of macrophages was increased in the adventitia and neointima. Staining for endothelial cells revealed a delay of re-endothelialization after radiation treatment.


CONCLUSIONS
Increased T-cell infiltration at the medial tear following IR, perhaps due to incomplete re-endothelialization, may indicate incomplete healing. The elevated apoptosis of these infiltrating T cells may indicate a mechanism for the resolution of inflammation.
Kollum
M
M
Cardiovascular Research Institute, Washington, DC, USA.
Cottin
Y
Y
Chan
R C
RC
Kim
H S
HS
Bhargava
B
B
Vodovotz
Y
Y
Waksman
R
R
D000199:Actins / Q000096:biosynthesis; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001918:Brachytherapy; D017252:CD3 Complex / Q000096:biosynthesis; D002452:Cell Count; D003331:Coronary Vessels / Q000166:cytology / Q000293:injuries* / Q000528:radiation effects*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D020287:In Situ Nick-End Labeling; D007496:Iridium Radioisotopes / Q000627:therapeutic use; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D013552:Swine; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000528:radiation effects*; D017539:Tunica Intima / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects
D000199:Actins; D017252:CD3 Complex; D007496:Iridium Radioisotopes