Delayed re-endothelialization and T-cell infiltration following intracoronary radiation therapy in the porcine model

Marc Kollum, Yves Cottin, Rosanna C. Chan, Han Soo Kim, Balram Bhargava, Yoram Vodovotz, Ron Waksman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)495-501
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume50
Issue number2
DOIs
StatePublished - 1 Jun 2001
Externally publishedYes

Keywords

  • Angioplasty
  • Brachytherapy
  • Leukocytes
  • Macrophages
  • Restenosis

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