Projects

Ján Maňka

Project selection:

National projects

ITAGES – Identification of stress-induced alterations in expression of NRF2 target genes in rat models of prehypertension: the effect of comorbid hypertriglyceridemia and dimethyl fumarate treatment
Identifikácia stresom vyvolaných zmien v expresii cieľových génov NRF2 v potkaních modeloch prehypertenzie: vplyv komorbidnej hypertriglyceridémie a liečby dimetylfumarátom
Program: SRDA
Duration: 1.7.2023 – 30.6.2027
Project leader: Ing. Maňka Ján, CSc.
Annotation: The nuclear transcription factor erythroid 2-related factor 2 (NRF2) is a key molecular link between several non-communicable diseases, as it regulates the expression of approximately 250 target genes, including those involvedin maintenance of redox balance, the development of metabolic disorders, cardiovascular and liver diseases, aswell as in immune responses. Borderline elevated blood pressure (prehypertension) is a common cardiovasculardisorder in humans, and elevated blood pressure has been found to be positively correlated with triglyceride levels.In addition, chronic stress is an etiological factor in the development of non-communicable diseases, includingelevated blood pressure and hypertriglyceridemia (HTG). In experimental studies, borderline hypertensive rats(BHR) and hypertriglyceridemic rats (HTGR) are suitable models of prehypertension without and with comorbidhypertriglyceridemia. These models are relevant for investigating the effects of stress as well as for investigatingthe role of changes in expression of NRF2 target genes in the development of hypertension associated withmetabolic diseases. To understand better the role of NFR2 as well as the impact of chronic social stress on thementioned diseased states, the aims of this project are: 1) to identify differences in expression of NRF2 targetgenes in two experimental models of prehypertension – without (in BHR) and with (in HTGR) comorbid HTG – incontrol conditions and during chronic social stress, 2) to determine if NRF2 activator dimethyl fumarate can reducestress-induced pathologies in prehypertensive rats, especially in those with comorbid HTG, and 3) to specify a setof suitable whole blood RNA biomarkers for evaluation of changes in NRF2 target genes in prehypertension andHTG and those genes altered by chronic social stress.