Platelet adhesion in atherogenesis

2.50
Hdl Handle:
http://hdl.handle.net/2436/98533
Title:
Platelet adhesion in atherogenesis
Authors:
Watkins, Jennifer
Abstract:
Platelets are known to play a key role in acute coronary events, such as myocardial infarction, associated with advanced atherosclerosis, but a number of papers have recently been published suggesting that platelet adhesion may initiate atherosclerotic lesion formation. The proposed research aimed to investigate this by seeing whether platelet adhesion occurred, directly or via leukocytes, to the endothelium in diabetic conditions. Diabetic-like conditions were chosen because an accelerated rate of lesion formation occurs. This was achieved by incubating endothelial cells with high concentrations of glucose and various types of AGEs. Bovine serum albumin of different purity, a peptide of albumin, and haemoglobin were glycated with D-glucose. Samples were taken at 2 weeks intervals to allow for determining the extent of glycation and allowing for investigation into whether the extent of glycation affected platelet adhesion. It also made possible analysis of extent of glycation, to see whether these have a relation to endothelial dysfunction (including cell proliferation, cell adhesion molecule expression, and ROS and cytokine production). There are discrepancies in the finding of studies looking into the effect of AGEs on the endothelium and there are no reported studies looking at cytokine production. As such, it was hoped that this research would allow for a greater understanding of the processes involved and whether endothelial dysfunction could account for accelerated lesion formation associated with diabetes. As a whole, the research intended to explore the hypothesis that platelet adhesion to the endothelium is required for foam cell formation and their development into atherosclerotic lesions. It aimed to see whether hyperglycaemia and the presence of high levels of AGEs induces endothelial dysfunction and therefore increases monocyte adhesion by the presence of activated platelets. In doing so, a greater understanding of the processes involved in accelerated lesion formation would allow for targeted research to allow for treatments to reduce foam cell deposition. This could be the use of a cocktail of anti-platelet drugs or ones that reduce endothelial dysfunction. This would reduce the manifestation of cardiovascular disease and therefore improve diabetic patient life as well as reduce the cost of treatment for the NHS, and therefore for the tax payer.
Advisors:
Vickers, James
Publisher:
University of Wolverhampton
Issue Date:
2010
URI:
http://hdl.handle.net/2436/98533
Type:
Thesis or dissertation
Language:
en
Description:
A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Master of Philosophy
Appears in Collections:
E-Theses

Full metadata record

DC FieldValue Language
dc.contributor.advisorVickers, Jamesen
dc.contributor.authorWatkins, Jenniferen
dc.date.accessioned2010-05-11T15:52:13Z-
dc.date.available2010-05-11T15:52:13Z-
dc.date.issued2010-
dc.identifier.urihttp://hdl.handle.net/2436/98533-
dc.descriptionA thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Master of Philosophyen
dc.description.abstractPlatelets are known to play a key role in acute coronary events, such as myocardial infarction, associated with advanced atherosclerosis, but a number of papers have recently been published suggesting that platelet adhesion may initiate atherosclerotic lesion formation. The proposed research aimed to investigate this by seeing whether platelet adhesion occurred, directly or via leukocytes, to the endothelium in diabetic conditions. Diabetic-like conditions were chosen because an accelerated rate of lesion formation occurs. This was achieved by incubating endothelial cells with high concentrations of glucose and various types of AGEs. Bovine serum albumin of different purity, a peptide of albumin, and haemoglobin were glycated with D-glucose. Samples were taken at 2 weeks intervals to allow for determining the extent of glycation and allowing for investigation into whether the extent of glycation affected platelet adhesion. It also made possible analysis of extent of glycation, to see whether these have a relation to endothelial dysfunction (including cell proliferation, cell adhesion molecule expression, and ROS and cytokine production). There are discrepancies in the finding of studies looking into the effect of AGEs on the endothelium and there are no reported studies looking at cytokine production. As such, it was hoped that this research would allow for a greater understanding of the processes involved and whether endothelial dysfunction could account for accelerated lesion formation associated with diabetes. As a whole, the research intended to explore the hypothesis that platelet adhesion to the endothelium is required for foam cell formation and their development into atherosclerotic lesions. It aimed to see whether hyperglycaemia and the presence of high levels of AGEs induces endothelial dysfunction and therefore increases monocyte adhesion by the presence of activated platelets. In doing so, a greater understanding of the processes involved in accelerated lesion formation would allow for targeted research to allow for treatments to reduce foam cell deposition. This could be the use of a cocktail of anti-platelet drugs or ones that reduce endothelial dysfunction. This would reduce the manifestation of cardiovascular disease and therefore improve diabetic patient life as well as reduce the cost of treatment for the NHS, and therefore for the tax payer.en
dc.language.isoenen
dc.publisherUniversity of Wolverhamptonen
dc.subjectPlateleten
dc.subjectAdhesionen
dc.subjectEndothelial dysfunctionen
dc.subjectAtherogenesisen
dc.subjectDiabetesen
dc.subjectAtherosclerosisen
dc.titlePlatelet adhesion in atherogenesisen
dc.typeThesis or dissertationen
dc.type.qualificationnameMPhilen
dc.type.qualificationlevelMasters Degreeen
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