Platelet function testing and the effect of natural products on platelet activation

Vucinic, L 2012, Platelet function testing and the effect of natural products on platelet activation, Doctor of Philosophy (PhD), Medical Sciences, RMIT University.


Document type: Thesis
Collection: Theses

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Title Platelet function testing and the effect of natural products on platelet activation
Author(s) Vucinic, L
Year 2012
Abstract Cardiovascular disease is still the main cause of morbidity and mortality in the world. Platelet activation is known to play a significant role in its initiation, progression and complications, and for this reason direct antiplatelet therapy is a major focus in the management of cardiovascular risk. However, in addition to platelet activation, factors such as decreased antioxidant status and increased reactive oxygen species, inflammation, dyslipidemia and sedentary lifestyle are also associated with poor cardiovascular outcomes.

Use of antiplatelet therapies for prevention of adverse cardiovascular events is accompanied with clinical resistance and side effects. There is a great need for improvement of treatment particularly when resistance is demonstrated. However the complex logistics behind platelet testing and available instrumentation represent a current obstacle. To overcome these limitations, we have developed a method of collecting, labelling and stabilizing blood collected by a finger-prick for immunophenotyping of platelets and platelet-leukocyte interactions by quantitative flow cytometry. We have demonstrated that this method is sensitive to inhibition of platelet function by standard antiplatelet therapy, and correlates well with standard laboratory techniques. The development of this technique allows platelet function testing without the need for venipuncture, and once stabilized the sample can be transported from the site of collection to the core facility for analysis up to 24 hours later, whereas standard diagnostic methods require analysis within 2-3 hours of collection.

Even though antiplatelet therapies improve morbidity and mortality, they inhibit both resting and activated platelets and disrupt normal process of haemostasis. This prompts for the investigations of natural products as alternatives for prevention or treatment of the cardiovascular disease.

We have demonstrated that the New Zealand Green Lipped mussel (Perna Canaliculus) extract, currently used as an anti-inflammatory agent, also inhibits platelet activation more effectively than standard fish oil formulations in a dose dependent manner. We have demonstrated that this is achieved, at least in part, by a novel mechanism of cyclo-oxygenase-1 independent inhibition of the thromboxane pathway of platelet activation, in addition to thromboxane-dependent inhibition common to other marine oils. This potent and novel antiplatelet mechanism may represent therapeutic potential for the use of Lyprinol in cardiovascular disease, but also represent a novel therapeutic target for next generation antiplatelet therapeutics.

While there is substantial evidence that exercise improves cardiovascular health, platelet activation increases after intensive exercise, representing a period of acute risk for cardiovascular events. In order to prevent this, we explored an antioxidant supplementation strategy aimed at ameliorating the reactive oxygen response. We have demonstrated that six weeks supplementation with high  and low  tocopherol decreases platelet hyperactivity and hypercoagulability due to increased oxidative stress caused by strenuous exercise in sedentary individuals better than α tocopherol or placebo. Supplementation with high γ tocopherol in combination with exercise reduces collagen-induced platelet aggregation below pre-exercise levels. Therefore γ tocopherol in the absence of high dose α tocopherol may enhance the beneficial effects of exercise. We have also demonstrated that γ tocopherol attenuates platelet function by inhibiting at least platelet cyclooxygenase-1 and arachidonic acid induced platelet activation.
Degree Doctor of Philosophy (PhD)
Institution RMIT University
School, Department or Centre Medical Sciences
Keyword(s) Cardiovascular disease
platelet activation
platelet function testing
platelet-leukocyte aggregates
Lyprinol
Perna Canaliculus
Vitamin E
γ-tocopherol
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