Therapeutic implications of bioactive nitrogen oxides in the triad of reno-cardio-metabolic disorders

BACKGROUND: Cardiovascular, metabolic and renal disorders are closely coupled and have major impact on global health.

Oxidative stress and impaired function of the nitric oxide (NO) signaling pathway have been implicated in development and progression of the disease and new strategies that correct redox balance and restore NO signaling may have major clinical implications.AIM: To explore and characterize the role of NADPH-oxidase-derived oxidative stress and NO signaling dysfunction in the triad of reno-cardio-metabolic disorders, and specifically investigate the therapeutic value of boosting an alternative route of NO formation, namely the nitrate-nitrite-NO pathway.WORK PLAN: In this project we use a translational approach that spans from mechanistic in vitro cell studies and sophisticated ex vivo microvascular studies to intervention studies with nitrate supplementation in animal disease models and in patients with cardio-metabolic disease as well as chronic kidney disease.SIGNIFICANCE: Preliminary data with stimulation of the nitrate-nitrite-NO pathway show promising effects in experimental studies and underlying mechanisms are being investigated.

Our studies in patients with reno-cardio-metabolic disorders show compromised NO signaling, and planned randomized trials with nitrate supplementation may have widespread and direct clinical relevance.