ESR 2: Tipparat Parakaw

Exploration of the therapeutic potential of dietary nitrate in platelet activity: role for XOR

Research project

Inorganic nitrate either via a dietary source or through nitrate salt supplementation inhibited platelet aggregation in healthy volunteers and hypercholesterolemic patients (Velmurugan 2013, PMID: 23806384, Velmurugan 2016, PMID: 26607938). Conversion of nitrate to nitrite by oral commensal bacteria, followed by entrance of this nitrite into the circulation to be converted to the potent vasodilator nitric oxide (NO) by specific nitrite reductases, occurs. In acute settings, a key vascular nitrite reductase is xanthine oxidoreductase (XOR) but whether it operates over long-term dietary intake is unknown.

The objective is to explore the functions of XOR in long-term dietary nitrate intake by using a genetic mouse model assessing cardiovascular function in wild type (control), Xdh heterozygous, and Xdh knock out mice. ESR 2 will focus on assessing platelet function under cardiovascular disease scenarios where the conventional pathways for endogenous NO generation are impaired, particularly hypertension. She will use measures of platelet aggregation in response to agonists using an aggregometer while p-selectin and platelet-leukocyte aggregates will be detected by flow cytometry. In addition, murine platelets response to ferric chloride will be determined using intravital microscopy and nitrate and nitrite blood levels as well as cGMP after long-term nitrate ingestion will be investigated in normotensive and hypertensive mice.

Main Supervisor

Name: Amrita Ahluwalia
Email: a.ahluwalia@qmul.ac.uk

Host Institution

Centre for Clinical Pharmacology
Barts and The London, Queen Mary's School of Medicine and Dentistry
Charterhouse Square
London, EC1M 6BQ
United Kingdom.

Planned secondment(s)

KI, Sweden (2019, 4 months)