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| Name | Class |
|---|---|
| AIDS Malignancy Consortium | NETWORK |
| Erasmus Medical Center | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High-LDL | patients with LDL cholesterol levels of >4.9 mmo/l, who have not been treated with statins in the past years, and who have an indication for treatment with statins. |
| |
| Control | control subjects with an LDL cholesterol level of <3.5 mmol/l |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| statin treatment | Drug | The patients with elevated LDL receive statin treatment in the context of normal patient care (so this is NOT an intervention of the study) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cytokine production capacity | Cytokine production capacity of PBMC's at baseline in patients with elevated and normal cholesterol levels | baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Cytokine production capacity | Cytokine production capacity of PBMC's at baseline in patients with elevated and normal cholesterol levels | Three months after start of statin treatment |
| Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes. |
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Inclusion Criteria:
Exclusion Criteria:
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Patients admitted to the outpatient clinics of the Radboudumc, AMC, or Erasmus MC, with LDL cholesterol levels >4.9 mmol/l, who will treated with statins according to current guidelines, will be will be selected.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud university medical center | Nijmegen | 6500 GA | Netherlands |
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| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| ID | Term |
|---|---|
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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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. | Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes. | Three months after start of statin treatment |