Journal article
Carbon monoxide and nitric oxide modulate alpha(2)-antiplasmin and plasmin activity: role of heme
Blood coagulation & fibrinolysis, v 22(8), pp 712-719
01 Dec 2011
PMID: 22024794
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 alpha(2)-antiplasmin via a putative heme group. Plasma, isolated alpha(2)-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 alpha(2)-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 alpha(2)-antiplasmin and plasmin. CO significantly enhanced alpha(2)-antiplasmin activity, but decreased plasmin activity. NO decreased both alpha(2)-antiplasmin and plasmin activity. Although inadequate LC-MS/MS data were obtained with alpha(2)-antiplasmin (secondary to glycosylation), a putative plasmin-associated heme was identified. CO elicits hypofibrinolysis by enhancing alpha(2)-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. Blood Coagul Fibrinolysis 22:712-719 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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Details
- Title
- Carbon monoxide and nitric oxide modulate alpha(2)-antiplasmin and plasmin activity: role of heme
- Creators
- Matthew R. Arkebauer - Drexel UniversitySri S. Kanaparthy - Drexel UniversitySaninuj N. Malayaman - Drexel UniversityKeith Vosseller - Drexel UniversityVance G. Nielsen - Drexel University
- Publication Details
- Blood coagulation & fibrinolysis, v 22(8), pp 712-719
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 8
- Grant note
- 4100054846 / Pennsylvania Department of Health Department of Anesthesiology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Anesthesiology and Perioperative Medicine
- Web of Science ID
- WOS:000297138400014
- Scopus ID
- 2-s2.0-84855191428
- Other Identifier
- 991019167880904721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Hematology