The main objective is to study whether patients with elevated levels of LDL show increased H3K4 trimethylation in the promoter regions of pro-inflammatory cytokines and have an augmented ex vivo TLR agonist-induced cytokine production in isolated…
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Epigenetic changes in the promotor regions of pro-inflammatory cytokines in
monocytes before and after statin treatment
Secondary outcome
cytokine release upon stimulation with TLR agonists and ex vivo
characterization of monocytes
Background summary
The innate immune system plays a pivotal role in the development and
progression of atherosclerosis. Recently, it was reported that monocytes can
develop a long-lasting immunological memory after stimulation with various
microorganisms, but also with oxidized LDL, which has been termed *trained
innate immunity*. This memory is induced by epigenetic reprogramming.
We hypothesize that trained monocytes augment atherogenesis. Intensive lipid
lowering with statins is capable of lowering plaque inflammation in patients at
high risk for cardiovascular events. In addition to their lipid lowering
effects, the pleiotropic effects of statins include lowering of inflammation.
Here we hypothesize that statins lower epigenetic changes in monocytes
responsible for increased inflammation.
Study objective
The main objective is to study whether patients with elevated levels of LDL
show increased H3K4 trimethylation in the promoter regions of pro-inflammatory
cytokines and have an augmented ex vivo TLR agonist-induced cytokine production
in isolated monocytes compared to control patients without atherosclerosis.
Next we will study the effect of Statins on the increased H3K4 trimethylation.
Study design
Observational study
Study burden and risks
There is no risk associated with participation. After signing for informed
consent, additional blood will be drawn for the ex vivo experiments
Geert Grooteplein Zuid 8
Nijmegen 6525GA
NL
Geert Grooteplein Zuid 8
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
Elevated levels of LDL in the blood (LDL >4.9 mmol/l)
Age > 18 years
Exclusion criteria
- Current lipid lowering treatment
- Previous cardiovascular events
- Known malignant disorders or any clinically significant medical condition that could interfere with the conduct of the study in the opinion of the investigator.
- Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
- Clinical signs of acute infection
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL50608.091.14 |