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Serotonin and platelet studies in vascular disease

Barradas, Manuel Antonio Mendonca; (1994) Serotonin and platelet studies in vascular disease. Doctoral thesis (Ph.D.), University College London (United Kingdom). Green open access

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Abstract

The aim of this thesis was to assess platelet function indices in peripheral vascular disease (PVD), diabetes mellitus, hypercholesterolaemia and renal disease in order to improve our understanding of the vascular complications associated with these conditions. Platelet shape change (PSC) in platelet-rich plasma (PRP) obtained from PVD patients was studied using a new sensitive and reproducible method. 5-hydroxytryptamine (5-HT)-induced PSC was diminished in PVD. This finding may be explained by desensitization, an effect which was reproduced in vitro using PRP from healthy subjects. The PSC methodology is likely to be more sensitive than platelet aggregation at detecting the inhibitory effects of drugs (e.g. naftidrofuryl; milrinone). An optimized method to assess whole blood platelet aggregation in PVD patients revealed enhanced aggregation to several platelet agonists. Aggregation induced by 5-HT and spontaneously was not affected by treatment with low dose aspirin (ASA) or by its addition in vitro. Intraplatelet 5-HT concentration in the above disease states was found to be diminished whereas concomitant plasma concentrations were raised. In renal and hypercholesterolaemic patients, a significant inverse correlation was found between intraplatelet 5-HT and plasma lipids. In hypercholesterolaemic patients, the intraplatelet 5-HT concentration was normalised following treatment with simvastatin, a cholesterol lowering drug. The plasma concentration of 5-HT was markedly elevated in PVD patients who developed graft stenosis; this elevation was partially corrected by low dose ASA. Release studies demonstrated that minor platelet activation (e.g. by stirring) causes significant 5-HT release, despite the absence of aggregation. 5-HT uptake was not affected by platelet activation. These findings may be relevant since 5-HT exerts effects on the vasculature (e.g. vasoconstriction, vascular smooth muscle proliferation). Furthermore, other anti-platelet drugs may be needed in addition to low dose ASA to further inhibit platelet aggregation, PSC and the release of intraplatelet contents.

Type: Thesis (Doctoral)
Qualification: Ph.D.
Title: Serotonin and platelet studies in vascular disease
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: (UMI)AAIU057197; Biological sciences; Health and environmental sciences; Platelet function
URI: https://discovery.ucl.ac.uk/id/eprint/10103012
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