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 Citations (Scopus)

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 2011
Externally publishedYes

Fingerprint

Antifibrinolytic Agents
Fibrinolysin
Carbon Monoxide
Heme
Nitric Oxide
Fibrinolysis
Thrombelastography
Thrombophilia
Nitric Oxide Donors
Tissue Plasminogen Activator
Enzymes
Glycosylation
Smoke
Tobacco Products
Liquid Chromatography
Mass Spectrometry
Smoking
Morbidity

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Carbon monoxide and nitric oxide modulate α2-antiplasmin and plasmin activity : Role of heme. / Arkebauer, Matthew R.; Kanaparthy, Sri S.; Malayaman, Saninuj N.; Vosseller, Keith; Nielsen, Vance G.

In: Blood Coagulation and Fibrinolysis, Vol. 22, No. 8, 12.2011, p. 712-719.

Research output: Contribution to journalArticle

Arkebauer, Matthew R. ; Kanaparthy, Sri S. ; Malayaman, Saninuj N. ; Vosseller, Keith ; Nielsen, Vance G. / Carbon monoxide and nitric oxide modulate α2-antiplasmin and plasmin activity : Role of heme. In: Blood Coagulation and Fibrinolysis. 2011 ; Vol. 22, No. 8. pp. 712-719.
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