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Restraint stress enhances arterial thrombosis in vivo - Role of the sympathetic nervous system


Stämpfli, Simon F; Camici, Giovanni G; Keller, Stephan; Rozenberg, Izabela; Arras, Margarete; Schuler, Beat; Gassmann, Max; Garcia, Irene; Lüscher, Thomas F; Tanner, Felix C (2014). Restraint stress enhances arterial thrombosis in vivo - Role of the sympathetic nervous system. Stress, 17(1):126-132.

Abstract

Stress is known to correlate with the incidence of acute myocardial infarction. However, the molecular mechanisms underlying this correlation are not known. This study was designed to assess the effect of experimental stress on arterial thrombus formation, the key event in acute myocardial infarction. Mice exposed to 20 hours of restraint stress displayed an increased arterial prothrombotic potential as assessed by photochemical injury-induced time to thrombotic occlusion. This increase was prevented by chemical sympathectomy performed through 6-hydroxydopamine (6-OHDA). Blood-born tissue factor activity was enhanced by stress and this increase could be prevented by 6-OHDA treatment. Vessel wall tissue factor, platelet count, platelet aggregation, coagulation times (PT, aPTT), fibrinolytic system (t-PA and PAI-1), and tail bleeding time remained unaltered. Telemetric analysis revealed only minor hemodynamic changes throughout the stress protocol. Plasma catecholamines remained unaffected after restraint stress. TNF-α plasma levels were unchanged and inhibition of TNF-α had no effect on stress-enhanced thrombosis. These results indicate that restraint stress enhances arterial thrombosis via the sympathetic nervous system. Blood-borne tissue factor contributes, at least in part, to the observed effect whereas vessel wall tissue factor, platelets, circulating coagulation factors, fibrinolysis, and inflammation do not appear to play a role. These findings shed new light on the understanding of stress-induced cardiovascular events.

Abstract

Stress is known to correlate with the incidence of acute myocardial infarction. However, the molecular mechanisms underlying this correlation are not known. This study was designed to assess the effect of experimental stress on arterial thrombus formation, the key event in acute myocardial infarction. Mice exposed to 20 hours of restraint stress displayed an increased arterial prothrombotic potential as assessed by photochemical injury-induced time to thrombotic occlusion. This increase was prevented by chemical sympathectomy performed through 6-hydroxydopamine (6-OHDA). Blood-born tissue factor activity was enhanced by stress and this increase could be prevented by 6-OHDA treatment. Vessel wall tissue factor, platelet count, platelet aggregation, coagulation times (PT, aPTT), fibrinolytic system (t-PA and PAI-1), and tail bleeding time remained unaltered. Telemetric analysis revealed only minor hemodynamic changes throughout the stress protocol. Plasma catecholamines remained unaffected after restraint stress. TNF-α plasma levels were unchanged and inhibition of TNF-α had no effect on stress-enhanced thrombosis. These results indicate that restraint stress enhances arterial thrombosis via the sympathetic nervous system. Blood-borne tissue factor contributes, at least in part, to the observed effect whereas vessel wall tissue factor, platelets, circulating coagulation factors, fibrinolysis, and inflammation do not appear to play a role. These findings shed new light on the understanding of stress-induced cardiovascular events.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
05 Vetsuisse Faculty > Institute of Laboratory Animal Science
04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:2014
Deposited On:22 Nov 2013 12:01
Last Modified:07 Dec 2017 23:55
Publisher:Taylor & Francis
ISSN:1025-3890
Additional Information:This is an Author's Accepted Manuscript of an article published in Stämpfli, Simon F; Camici, Giovanni G; Keller, Stephan; Rozenberg, Izabela; Arras, Margarete; Schuler, Beat; Gassmann, Max; Garcia, Irene; Lüscher, Thomas F; Tanner, Felix C (2013). Restraint stress enhances arterial thrombosis in vivo - Role of the sympathetic nervous system. Stress:Epub ahead of print. copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.3109/10253890.2013.862616.
Publisher DOI:https://doi.org/10.3109/10253890.2013.862616
PubMed ID:24215418

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