TY - JOUR
T1 - Delayed re-endothelialization and T-cell infiltration following intracoronary radiation therapy in the porcine model
AU - Kollum, Marc
AU - Cottin, Yves
AU - Chan, Rosanna C.
AU - Kim, Han Soo
AU - Bhargava, Balram
AU - Vodovotz, Yoram
AU - Waksman, Ron
PY - 2001/6/1
Y1 - 2001/6/1
N2 - Purpose: To evaluate the late induction of apoptosis following intracoronary radiation (IR) and the effects of IR on inflammatory cells. Methods and Materials: 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 α-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. Conclusion: 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.
AB - Purpose: To evaluate the late induction of apoptosis following intracoronary radiation (IR) and the effects of IR on inflammatory cells. Methods and Materials: 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 α-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. Conclusion: 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.
KW - Angioplasty
KW - Brachytherapy
KW - Leukocytes
KW - Macrophages
KW - Restenosis
UR - http://www.scopus.com/inward/record.url?scp=0035370310&partnerID=8YFLogxK
U2 - 10.1016/S0360-3016(01)01497-3
DO - 10.1016/S0360-3016(01)01497-3
M3 - Article
C2 - 11380239
AN - SCOPUS:0035370310
SN - 0360-3016
VL - 50
SP - 495
EP - 501
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -