ESR9
ESR 9: Chiara Moretti
The Nitrate-Nitrite-Nitric Oxide Pathway: Impact on Cardiovascular and Metabolic Function
Research project
The small gaseous molecule nitric oxide (NO) represents a key signaling messenger in the cardiovascular system and reduced NO signaling is correlated with a wide range of well-known risk factors for the most common cardiovascular diseases (CVDs).
The production of nitric oxide is ensured by different nitric oxide synthases and occurrs through the oxidation of the amino acid L-arginine. However, a more recently discovered pathway leading to NO production, consists of serial reductions of the inorganic anion nitrate (NO3-) and nitrite (NO2-). Both anions are abundant in the diet, especially in green leafy vegetables and beetroot.In the past few years, several findings have confirmed that mitochondria represent a target for NO and related nitrogen oxides and that a nitrate supplemented diet is able to improve mitochondrial efficiency and may have implications for the treatment of dysfunctional mitochondria-related diseases. In these pathologies as well as in aging, mitochondrial impairment and increased reactive oxygen species (ROS) production play a central role. In this regard, studies show that nitrate/nitrite are able to limit superoxide generation and damage. Furthermore, xanthine oxidase (XO), also known as a superoxide-producing enzyme, has been proved to mediate some of the protective effects of nitrate/nitrite by catalyzing their reduction to NO.
ESR 9 will investigate the role of dietary nitrate and xanthine oxidase in models of cardiovascular and metabolic disease. In parallel, the effects of nitrate and nitrite on metabolic function, ROS formation and lifespan will be investigated in Drosophila melanogaster and aged mice.
Main Supervisor
Name: Jon Lundberg
Email: Jon.Lundberg@ki.se
Host Institution
Department of Physiology and Pharmacology (FYFA), C3
Pharmacological Nitric Oxide Research
Karolinska Institutet
171 77 Stockholm
Sweden
Expected Results
- Correlate the improved mitochondrial efficiency and the decrease in ROS production exerted by nitrate with its positive effects on disease.
- Clarify the role of mitochondria and XO-mediated NO formation in any protective effects of dietary nitrate.
Planned secondment(s)
- QMUL, United Kingdom (2019): To study engagement of XOR in the effects studied in models of renal hypertension.
- Genomics England, United Kingdom (2019): To train on how to engage patients and clinicians in research projects.
