Atherosclerosis
Conditions
Brief 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, which has been termed 'trained innate immunity'. This memory is induced by epigenetic reprogramming, in particular trimethylation of lysine 4 at histone 3 (H3K4me3). In this study, the investigators aim to investigate the immunophenotype of circulating monocytes in patients with elevated LDL cholesterol levels and the effect of statins on this phenotype.
Detailed description
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, which has been termed 'trained innate immunity'. This memory is induced by epigenetic reprogramming, in particular trimethylation of lysine 4 at histone 3 (H3K4me3). The main objective is to study whether circulating monocytes of patients with elevated levels of LDL have a phenotype of trained innate immunity compared to control patients. Subsequently the investigators will study the effect of treatment with statins on the increased inflammatory response and epigenetic changes of the innate immune system.
Interventions
DRUGstatin treatment
The patients with elevated LDL receive statin treatment in the context of normal patient care (so this is NOT an intervention of the study)
Sponsors
AIDS Malignancy Consortium
Erasmus Medical Center
Radboud University Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Aged 18 years or older * Elevated LDL levels (\>4.9 mmol/l) * Decision made by treating physician to initiate statin treatment
Exclusion criteria
* previous cardiovascular events.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cytokine production capacity | baseline | Cytokine production capacity of PBMC's at baseline in patients with elevated and normal cholesterol levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cytokine production capacity | Three months after start of statin treatment | Cytokine production capacity of PBMC's at baseline in patients with elevated and normal cholesterol levels |
| Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes. | baseline | Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes. |
Countries
Netherlands
Outcome results
None listed