Mattias Carlström group projects
Presentation of the group's Pre-Clinical and Clinical studies.
Pre-Clinical Studies
1. Effects of nitrate, and underlying mechanisms, in models of reno-cardio-metabolic disorders
Hypothesis: Supplementation with nitrate improves renal, cardiovascular and metabolic functions by reducing SNA and NOX, as well as by modulation of mitochondrial function and inflammatory responses.
2. Effects of dietary nitrate supplementation in type 2 diabetes and associated liver steatosis
Overall aim and hypothesis: To explore the therapeutic potential of dietary nitrate in T2D and associated liver steatosis, and further investigate the underlying mechanisms. Our hypothesis is that supplementation with inorganic nitrate can restore NO bioavailability to maintain cardiometabolic homeostasis.
3. The role of the oral microbiome in nitrate bioactivation
Hypothesis: Oral commensal bacteria are vital for mediating the bioactivation of nitrate, and its associated favorable cardio-metabolic effects.
Clinical Studies
1. Effects of inorganic nitrate in healthy subjects and in hypertensive patients with CKD
Hypothesis: Nitrate attenuates hypertension and improves renal and metabolic functions
2. Effects of inorganic nitrate in healthy subjects and patients with advanced CKD and dialysis
Hypothesis: Nitrate attenuates hypertension and improves quality of life parameters
3. Effects of nitrate supplementation in women with pre-eclampsia and gestational diabetes
Hypothesis 1: Pre-eclampsia (PE) and gestational diabetes (GD) is associated with oxidative stress and reduced NO bioavailability, which increase their cardiovascular risk
Hypothesis 2: Nitrate treatment restores NO bioavailability and reduces cardiovascular risk in PE.
4. Effects of short term mouthwash on cardio-metabolic functions
Hypothesis 1: Eradication of commensal oral bacteria can worsen cardio-metabolic functions
5. Effects of nitrate supplementation in patients with type 2 diabetes
Hypothesis: Nitrate treatment improve insulin/glucose homeostasis, lower blood pressure and improve kidney function in patients with T2D.
Significance
CVD, T2D and associated renal disease are major global health problems. Advanced age and unhealthy dietary habits contribute to the increasing incidence. Further mechanistic understandings will greatly aid in the development of new strategies to prevent development or progression of disease. We propose that imbalance between the generation of O2- and NO in the microvasculature is a central pathogenic event, leading to oxidative stress, mitochondrial dysfunction and progressive inflammation. Specifically, we investigate the therapeutic value of bioactive nitrogen oxide species including NO, being formed following nitrate supplementation, and investigate underlying mechanisms.
High intake of vegetables lowers the risk of CVD and T2D, but the mechanisms are not yet clear. We suggest that these effects, at least in part, may be explained by stimulation of a nitrate-nitrite-NO pathway. Our preliminary findings with nitrate supplementation are promising, suggesting that dietary nitrate supplementation can prevent reno-cardio-metabolic pathologies via mechanism(s) that involve reduction of oxidative stress and restoration of NO signaling. Our studies in patients with CVD and advanced kidney disease show compromised NO signaling, and planned studies with nitrate supplementation (also in T2D patients) may have widespread and direct clinical relevance.