Carbon Monoxide and Nitric Oxide Induced-Heme-Based Modification of Alpha-2-Antiplasmin and Plasmin Activity

Publication Year:
2011
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Repository URL:
https://digitalcommons.pcom.edu/biomed/3; https://digitalcommons.pcom.edu/cgi/viewcontent.cgi?article=1006&context=biomed
Author(s):
Arkebauer, Matthew R.
Tags:
Smoking; Tobacco; Carbon Monoxide; Fibrinolysis; Biochemistry; Medicine and Health Sciences
thesis / dissertation description
Objectives: Carbon monoxide (CO) derived from cigarette smoke or released from carbon monoxide releasing-molecule 2 (CORM-2), diminishes fibrinolysis. The primary purpose of this study was to determine if CO diminished fibrinolysis by means of enhancing α2-antiplasmin via an alleged heme group. Methods: Plasma, isolated α2-antiplasmin and isolated plasmin were exposed to CO released from CORM-2 (tricarbonyldichlororuthenium (II) dimer) and nitric oxide (NO) via a NO donor to induce carboxyheme and metheme states. 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, see Table 1) was used to identify heme released from α2-antiplasmin and plasmin. Results: CO significantly enhanced α2-antiplasmin activity but decreased plasmin activity. NO decreased both α2-antiplasmin and plasmin activity. While ii insufficient LC-MS/MS data was obtained with α2-antiplasmin (secondary to glycosylation), a putative plasmin-associated heme was identified. Conclusion: CO causes hypofibrinolysis by enhancing α2-antiplasmin activity and decreasing plasmin activity. Based on responses to NO and LCMS/ MS data, it is highly likely that both enzymes are modulated by attached heme groups. Attempts 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.