Carbon monoxide and nitric oxide modulate α2-antiplasmin and plasmin activity: Role of heme

Matthew R. Arkebauer, Sri S. Kanaparthy, Saninuj N. Malayaman, Keith Vosseller, Vance G. Nielsen

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Cigarette smoke and carbon monoxide (CO) released from tricarbonyldichlororuthenium (II) dimer (CORM-2) attenuate fibrinolysis. The purpose of the present study was to determine whether CO diminished fibrinolysis by enhancement of α2-antiplasmin via a putative heme group. Plasma, isolated α2-antiplasmin and isolated plasmin were exposed to CO released from CORM-2 and nitric oxide (NO) via a NO donor to induce carboxyheme and metheme states, respectively. Exposed, isolated enzymes were placed in either α2-antiplasmin-deficient or normal plasma. Effects of CO and NO on tissue-type plasminogen activator initiated fibrinolysis were determined by thrombelastography. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to identify heme released from α2-antiplasmin and plasmin. CO significantly enhanced α2-antiplasmin activity, but decreased plasmin activity. NO decreased both α2-antiplasmin and plasmin activity. Although inadequate LC-MS/MS data were obtained with α2-antiplasmin (secondary to glycosylation), a putative plasmin-associated heme was identified. CO elicits hypofibrinolysis by enhancing α2-antiplasmin activity and decreasing plasmin activity. On the basis of the responses to NO and LC-MS/MS data, it is highly likely that both enzymes are modulated by attached heme groups. Efforts to develop methods to detect CO-mediated hypercoagulability are ongoing, with the goal of identifying populations at risk of thrombotic morbidity secondary to cigarette smoking.

Original languageEnglish (US)
Pages (from-to)712-719
Number of pages8
JournalBlood Coagulation and Fibrinolysis
Volume22
Issue number8
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Keywords

  • Carbon monoxide-releasing molecule
  • Heme
  • Plasmin
  • Thrombelastography
  • α2-antiplasmin

ASJC Scopus subject areas

  • Hematology

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