PhD position in medical science-Importance of Plasminogen for atherosclerosis

Employer
Sahlgrenska academy
Location
Sweden
Posted
April 20 2016
Position Type
Full Time
Thromboembolic vascular events, including myocardial infarction ischemic stroke, are major causes of global mortality and morbidity. Atherosclerosis, which most often is the underlying cause of an acute thrombus formation, is a chronic disease developing over decades. Endothelial function is essential for vascular homeostasis and progressive impairment is an early step in the developing process of atherosclerosis. The plasminogen-plasmin (P-P) system is an important biological system that is involved in various aspects of endothelial function. The system comprises an inactive circulating proenzyme, plasminogen, which can be converted to the active enzyme, plasmin, by plasminogen activators (t-PA and u-PA). Inhibition of the system is mainly by specific plasminogen activator inhibitors (PAIs). The traditional role of the P-P-system is to regulate the expansion of blood clots in vivo. However over the last years the P-P system has been found to be involved in a more diverse set of biological functions including development of atherosclerosis, vasculogenesis, etc. u-PA gene deficient mice have impaired healing of arterial wall injuries. PAI-1 deficient mice demonstrate an increased smooth muscle cell proliferation after vascular injury. tPA has recently been described to mediate migration and extravasation of various subsets of inflammatory cells,. We have recently discovered the t-PA is under strict epigenetic control. However if this even is true for the other factors of the P-P-system is still not known.



We hypothesize that the P-P-system has previously unrecognized roles as regulators of inflammatory cell recruitment and endothelial regeneration in areas of endothelial remodelling, and that tPA in this setting is regulated by dynamic DNA methylation. The aim of this doctoral project will be to map the expression of fibrinolytic proteins in endothelial cells in vivo during different stages of atherosclerosis. To investigate if tPA is involved in recruiting leukocytes to sites of endothelial remodeling and if it is under epigenetic control. From a clinical perspective the P-P-system may be a new interesting target to facilitate re-endothelialisation after vessel injury as well as to prevent or delay formation of atherosclerotic plaques.



For more information about the position and entry requirements visit the announcement on the application website: http://www.gu.se/english/about_the_university/announcements-in-the-job-application-portal/ For more information about the project please contact the main supervisor Niklas Bergh, Institute of Medicine, email: niklas.bergh@gu.se

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