The origin of post-injury neointimal cells in the rat balloon injury model

Luis Rodriguez-Menocal, Melissa St-Pierre, Yuntao Wei, Sheik Khan, Dania Mateu, Marian Calfa, Amir A. Rahnemai-Azar, Gary Striker, Si M. Pham, Roberto I Vazquez-Padron

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Abstract

Aims: The origin of post-injury neointimal cells is still a matter of debate. This study aims to determine the anatomic source of neointimal cells in one of the most important animal models for the study of vascular stenosis in response to injury, the rat balloon injury model. Methods and results: Chimeric rats were generated by rescuing lethally irradiated animals with green fluorescent protein (GFP)+ bone marrow (BM) cells from transgenic rats. Neointimal formation was induced in the right iliac artery of these animals using a balloon angioplasty catheter. Injured and non-injured contra-lateral arteries were harvested at 7, 14, and 30 days post-surgery. BM-derived monocytes/macrophages (CD68+ GFP+) were abundant in the media and adventitia of injured vessels harvested at 7 days as determined by immunofluorescence and confocal microscopy. The number of GFP + cells declined in the vascular wall with time. Post-injury neointimal cells were mostly GFP-/smooth muscle actin (SMA) +, which indicated that those cells originated in the recipient. Only a few neointimal cells seemed to come from circulating progenitors (GFP + SMA+, 2.34% ± 1.61). The vascular origin of cells in the neointima was further confirmed by transplanting injured GFP arteries into wild-type recipients. In these grafts, 94.23 ± 0.44% of medial and 92.95 ± 19.34% of neointimal cells were GFP+ SMA+. Finally, we tested the capacity of vascular smooth muscle cells (VSMC) to migrate through the vascular wall using a novel in vivo assay. As expected, VSMC migrated and populated the neointima only in response to injury. Conclusion: Our results suggest that neointimal cells in the rat balloon injury model mostly derive from pre-existing vascular cells and that only a small population of those cells come from BM-derived progenitors.

Original languageEnglish
Pages (from-to)46-53
Number of pages8
JournalCardiovascular Research
Volume81
Issue number1
DOIs
StatePublished - Jan 1 2009

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Green Fluorescent Proteins
Wounds and Injuries
Blood Vessels
Smooth Muscle
Actins
Neointima
Vascular Smooth Muscle
Bone Marrow Cells
Smooth Muscle Myocytes
Arteries
Transgenic Rats
Adventitia
Balloon Angioplasty
Iliac Artery
Ambulatory Surgical Procedures
Fluorescence Microscopy
Confocal Microscopy
Monocytes
Pathologic Constriction
Catheters

Keywords

  • Angioplasty
  • Balloon injury
  • Cell origin
  • Neointima
  • Rat
  • Restenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

The origin of post-injury neointimal cells in the rat balloon injury model. / Rodriguez-Menocal, Luis; St-Pierre, Melissa; Wei, Yuntao; Khan, Sheik; Mateu, Dania; Calfa, Marian; Rahnemai-Azar, Amir A.; Striker, Gary; Pham, Si M.; Vazquez-Padron, Roberto I.

In: Cardiovascular Research, Vol. 81, No. 1, 01.01.2009, p. 46-53.

Research output: Contribution to journalArticle

Rodriguez-Menocal, L, St-Pierre, M, Wei, Y, Khan, S, Mateu, D, Calfa, M, Rahnemai-Azar, AA, Striker, G, Pham, SM & Vazquez-Padron, RI 2009, 'The origin of post-injury neointimal cells in the rat balloon injury model', Cardiovascular Research, vol. 81, no. 1, pp. 46-53. https://doi.org/10.1093/cvr/cvn265
Rodriguez-Menocal L, St-Pierre M, Wei Y, Khan S, Mateu D, Calfa M et al. The origin of post-injury neointimal cells in the rat balloon injury model. Cardiovascular Research. 2009 Jan 1;81(1):46-53. https://doi.org/10.1093/cvr/cvn265
Rodriguez-Menocal, Luis ; St-Pierre, Melissa ; Wei, Yuntao ; Khan, Sheik ; Mateu, Dania ; Calfa, Marian ; Rahnemai-Azar, Amir A. ; Striker, Gary ; Pham, Si M. ; Vazquez-Padron, Roberto I. / The origin of post-injury neointimal cells in the rat balloon injury model. In: Cardiovascular Research. 2009 ; Vol. 81, No. 1. pp. 46-53.
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