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Title: Thrombotic and endothelial factors in the control of human vascular function
Author: Lang, Ninian Nicholas
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2009
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Objectives: 1) To assess the role of gap junctions and their connexin components in endothelium-derived hyperpolarising factor (EDHF)-mediated vasorelaxation in human resistance arteries in vitro. 2) To evaluate the vascular effects of potentiation of communication via the connexin 43 gap junction subunit in vivo. 3) To evaluate the role of the endothelium and endothelium-derived factors in the mediation of PAR-1 evoked vasomotion and t-PA release in vivo. 4) To examine the effect of cigarette smoking upon endothelial PAR-1 responses in vivo. Conclusions: Connexin 43 is vital for the mediation of EDHF activity in pregnant human resistance vessels in vitro. However, augmentation of connexin 43 communication has no effect on arterial vasodilatation or t-PA release in the peripheral circulation of healthy man. It remains to be established whether augmentation of connexin 43 communication improves endothelial function in patients with vascular disease. Acting via PAR-1, thrombin makes a major interaction with arterial, but not venous, endothelium to cause vasodilatation via nitric oxide- and EDHF-dependent pathways. It causes the endothelial release of t-PA that is independent of prostacyclin, nitric oxide and EDHF. The arterial effects of PAR-1 activation are markedly impaired in association with endothelial dysfunction caused by smoking cigarettes. Relative arterial stasis and near abolition of t-PA release will strongly promote clot propagation and vessel occlusion. These findings highlight the important interaction between thrombotic and endothelial factors at times of acute arterial injury such as occurs during acute myocardial infarction and stroke.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available