C5b-9 terminal complement complex assembly on apoptotic cells in human arterial wall with atherosclerosis

Exp Mol Pathol. 2004 Feb;76(1):17-23. doi: 10.1016/j.yexmp.2003.10.002.

Abstract

Apoptosis plays an important role in atherosclerosis. The factors regulating this process are not well defined. We examined the relation of apoptotic cells with the terminal complement complex C5b-9 in human atherosclerotic lesions. The extent of apoptosis was determined using TdT dUTP nick-end labeling (TUNEL) and immunohistochemistry of apoptosis regulators caspase-3, caspase-9, Bax, and Bcl-2. C5b-9 was localized by immunohistochemistry and immunoelectron microscopy. The apoptotic index was higher in fibrous plaques when compared with intimal fatty streaks and intimal thickenings. Bax expression was present in TUNEL+ apoptotic cells, and Bcl-2 was rarely present in the atherosclerotic wall. Active caspase 9 and caspase 3 deposits were present in the same areas, suggesting an involvement of the mitochondrial pathway. C5b-9 deposits colocalized with TUNEL+ cells, and the percent of double-positive cells was 2% in fatty streaks, 12% in intimal thickenings, and 35% in fibrous plaques. Colocalization of apoptotic cells with C5b-9 was also confirmed by immunoelectron microscopy. In conclusion, some apoptotic cells carry C5b-9 deposits, suggesting that complement might be activated by apoptotic cells and involved in the promotion of apoptosis, contributing to the progression of atherosclerotic lesions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aorta / anatomy & histology
  • Aorta / metabolism*
  • Aorta / pathology
  • Apoptosis / physiology*
  • Arteriosclerosis / metabolism*
  • Caspase 3
  • Caspase 9
  • Caspases / metabolism
  • Complement Membrane Attack Complex / metabolism*
  • Femoral Artery / metabolism
  • Femoral Artery / ultrastructure
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immunoenzyme Techniques
  • In Situ Nick-End Labeling
  • Microscopy, Immunoelectron
  • Middle Aged
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • Complement Membrane Attack Complex
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Caspases