Fas-mediated apoptosis in accelerated graft arteriosclerosis

Nicanor I. Moldovan, Zhiping Qian, Yong Chen, Chunming Dong, Anita Ying, Ralph H. Hruban, Nicholas A. Flavahan, William M. Baldwin, Fred Sanfilippo, Pascal J. Goldschmidt-Clermont

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Pathological conditions have been recognized where vessel destruction is a prominent feature of the pathogenic process. One such condition consists of the chronic rejection of blood vessels in transplanted solid organs. Accelerated graft arteriosclerosis (AGA) is a multifactorial process characterized by the concentric proliferation of smooth muscle cells (SMCs) within the intima of the vessel wall of transplanted organs. Proliferation of SMCs within the intima corresponds to a response of these cells to injury. In situations like restenosis post-angioplasty, the mechanism of injury: the mechanical disruption of the tunica media, is evident. However, in the case of AGA, the mechanism of injury has remained elusive. In this report, we provide evidence that injury to SMCs in AGA vessels requires an intact Fas pathway. The resulting damage to the tunica media and internal elastic lamina, in turn, might trigger the proliferation of intimal smooth muscle cells that appear to be less sensitive to Fas mediated killing, particularly when supported by a favorable context of inflammatory cytokines and growth factors, as it is the case in AGA. This pathogenic process results in a absolute loss of functional blood vessels that is not being compensated by an efficient angiogenic response.

Original languageEnglish (US)
Pages (from-to)245-254
Number of pages10
JournalAngiogenesis
Volume2
Issue number3
DOIs
StatePublished - Jan 1 1998

Keywords

  • Apoptosis
  • Chronic rejection
  • Fas
  • Fas-ligand
  • Ipr
  • Smooth muscle cells
  • Transplant
  • Vasculopathy

ASJC Scopus subject areas

  • Cancer Research
  • Clinical Biochemistry
  • Polymers and Plastics
  • Pathology and Forensic Medicine

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