Histologic evidence of foreign body granulation tissue and de novo lesions in patients with coronary stent restenosis

Cardiology. 1999;92(3):171-7. doi: 10.1159/000006967.


Objectives: We examined the relative contributions of foreign body granulation and de novo lesions to neointimal hyperplasia in atherectomized specimens of restenosis after coronary stenting.

Background: Clinicopathological studies have suggested that smooth muscle cell (SMC) hyperplasia is the most likely cause of restenosis after coronary stenting. It is not yet fully understood how SMC hyperplasia occurs or how SMCs stimulation can lead to intimal hyperplasia. Although inflammation has been postulated to be a major contributor to restenosis after coronary stenting, there is a paucity of data on the relationsip between inflammation and subsequent neointimal formation in humans. Only in a porcine experimental model of stent restenosis, foreign body granulation tissue as a cause of inflammation in stent restenosis was reported.

Methods: Tissue specimens were retrieved by directional atherectomy from 11 patients in whom stent restenosis developed after percutaneous revascularization of coronary artery disease. For specimens preserved in 10% buffered formalin, analysis of cellular composition was performed quantitatively after cell-specific immunostaining, i.e. CD68, UCHL-1, HLA-DR, smooth muscle actin, vimentin, desmin, PCNA and TGF-beta.

Results: Five of the 11 patients showed granulation tissues 3-6 months after stent implantation, of whom 3 patients revealed foreign body multinucleated giant cells around the stent struts where PCNA- and vimentin-positive SMCs were demonstrated. Calcification and de novo lesions in medial and adventitial tissues were observed in 3 other patients, and fresh and/or organized thrombi were documented in 3 of the 11 patients.

Conclusions: These findings support the notion that stent restenosis results from SMC hyperplasia and suggest that the foreign body granulation tissue against metals of the stents and de novo lesions could play an important role in chronic inflammation leading to intimal hyperplasia and subsequently to stent restenosis in some patients. Clinicians should thus consider whether a patient may be allergic to stent components with unknown reaction, e.g. haptens.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherectomy, Coronary
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Calcinosis / metabolism
  • Calcinosis / pathology
  • Coronary Angiography
  • Coronary Disease / diagnostic imaging
  • Coronary Disease / surgery*
  • Female
  • Giant Cells, Foreign-Body / metabolism
  • Giant Cells, Foreign-Body / pathology*
  • Graft Occlusion, Vascular / metabolism
  • Graft Occlusion, Vascular / pathology*
  • Graft Occlusion, Vascular / surgery
  • Granuloma, Foreign-Body / metabolism
  • Granuloma, Foreign-Body / pathology*
  • Granuloma, Foreign-Body / surgery
  • HLA-DR Antigens / metabolism
  • Humans
  • Hyperplasia
  • Immunoenzyme Techniques
  • Male
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Recurrence
  • Reoperation
  • Stents*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Transforming Growth Factor beta / metabolism
  • Tunica Intima / pathology*


  • HLA-DR Antigens
  • Microfilament Proteins
  • Proliferating Cell Nuclear Antigen
  • Transforming Growth Factor beta