Cardiolipin-protein complexes and initiation of complement activation after coronary artery occlusion

R. D. Rossen, L. H. Michael, H. K. Hawkins, K. Youker, W. J. Dreyer, R. E. Baughn, M. L. Entman

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Specific rabbit anti-cardiolipin (anti-CL) antibodies were used to investigate the hypothesis that cardiolipin, associated with mitochondrial membrane proteins, binds C1 and facilitates activation of the complement cascade following reperfusion of ischemic myocardium. By immunoelectron microscopy, anti-CL localized to subsarcolemmal mitochondria, emerging through breaks in membranes of damaged cardiac myocytes. Anti-CL reacted with > 15 mitochondrial constituents, most of which comigrated with the proteins that bind C1q in transblots of subsarcolemmal mitochondria, fractionated by polyacrylamide gel electrophoresis under reducing conditions in the presence of sodium dodecyl sulfate. A subset of the C1q-binding proteins >24 to 37 kD served as stable sites for assembly of C3, C5, and C9. Cardiac lymph, collected during the first hour after reperfusion of ischemic myocardium, contained proteins of diverse size that reacted with both anti-CL and C1q. Cardiac lymph, collected before occlusion and 4 to 5 hours after reperfusion, in comparison, had few if any C1q or anti-CL reactive proteins. Treatment with phospholipase suppressed the C1q-binding activity and anti-CL reactivity of the proteins in reperfusion lymph and those with similar properties in mitochondrial extracts. Our data suggest that during ischemia, mitochondria, extruded through breaks in the sarcolemma, unfold and release membrane fragments in which cardiolipin and protein are intimately associated. By binding C1 and supplying sites for the assembly of later-acting complement components, these fragments provide the means to disseminate the complement- mediated inflammatory response to ischemic injury.

Original languageEnglish (US)
Pages (from-to)546-555
Number of pages10
JournalCirculation Research
Volume75
Issue number3
StatePublished - Sep 1994
Externally publishedYes

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Keywords

  • cardiolipin
  • coronary artery occlusion
  • ischemia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Rossen, R. D., Michael, L. H., Hawkins, H. K., Youker, K., Dreyer, W. J., Baughn, R. E., & Entman, M. L. (1994). Cardiolipin-protein complexes and initiation of complement activation after coronary artery occlusion. Circulation Research, 75(3), 546-555.