Therapeutic implications of bioactive nitrogen oxides in reno-cardiovascular and metabolic disorders

Background: Cardiovascular, metabolic, and renal disorders are closely interconnected, largely shaped by our lifestyle (physical inactivity & unhealthy diet), which often lead to obesity, and they profoundly impact global health.

Oxidative stress and impaired nitric oxide (NO) signaling contribute to disease development and progression, highlighting the potential of new strategies to rebalance redox levels and restore NO generation and downstream signaling.Aim: To explore the role and regulation of NADPH oxidase-derived oxidative stress and impaired NO signaling in the triad of reno-cardiovascular and metabolic disorders.

Specifically, we investigate the therapeutic value of boosting the generation of bioactive nitrogen oxide species, including NO.Work Plan: Our translational approach encompasses mechanistic in vitro cell studies, sophisticated ex vivo microvascular studies, and intervention studies evaluating nitrate treatment in animal disease models and patients with cardiovascular disease, chronic kidney disease, and type 2 diabetes.Significance: Our preliminary data show promising effects of stimulation of the nitrate-nitrite-NO pathway in experimental models, and underlying mechanisms are currently investigated.

Furthermore, our findings of compromised NO signaling in patients with reno-cardiovascular and metabolic disorders highlight the potential clinical significance of ongoing and planned randomized trials involving nitrate treatment outlined in this proposal.