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Title: The role of reactive nitrogen species and aged garlic extract on platelet function
Author: Smith, Sarah
ISNI:       0000 0004 5350 5061
Awarding Body: Liverpool John Moores University
Current Institution: Liverpool John Moores University
Date of Award: 2014
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Natural therapies such as Aged Garlic Extract (AGE) have displayed cardioprotective properties, with studies indicating that AGE can inhibit platelet aggregation both in vivo and in vitro. The mechanism of inhibition induced by AGE is proposed to be due to AGE exerting effects upon several targets within platelets, including calcium and cyclic adenosine monophosphate (cAMP). The effect of AGE upon the other cyclic nucleotide, cyclic guanosine monophosphate (cGMP) is currently unknown. The aims therefore of this project are to identify the effect of AGE upon platelet cGMP, as well as associated signaling molecules including nitric oxide (NO) and cAMP.It was found that the NO donor 3-morpholinosydnonimine (Sin-1) in high concentrations along with the presence of specific inhibitors inhibited platelet aggregation independently of cGMP. Experimentation using chemical inhibitors also displayed erratic results in the presence of high concentrations of AGE, indicating that AGE was influencing the binding of such inhibitors. The results of in vitro experiments indicated that AGE moderately increases intraplatelet cGMP, whereas intraplatelet cAMP is significantly increased. it is proposed that the main mechanism of inhibition caused by AGE is due to increases in cAMP. As intraplatelet cAMP can also be influenced by intraplatelet cGMP, it is likely that cAMP is increased directly and indirectly by AGE.Evidence provided in the present study supports the proposed theory that the mechanisms of inhibition of platelet aggregation by AGE is multimechanistic. More specifically inhibition of platelet aggregation by AGE is due to AGE increasing intraplatelet cyclic nucleotides, reducing the expression of key receptors such as GPIIb/IIIa and inhibiting agonist induced platelet shape change. As AGE can inhibit platelet aggregation, which is a key risk factor in cardiovascular disease, the consumption of AGE would be beneficial to those who are at risk of cardiovascular episodes.
Supervisor: Rahman, Khalid; Lowe, Gordon Sponsor: Wakunaga of America Ltd
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: nitric oxide ; platelets ; garlic ; phytochemicals ; nutraceuticals ; cardiovascular disease