Related Experiment Video
Updated: Jan 7, 2026
LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
Published on: November 17, 2018
Innate immune cell function in statin-treated patients with severe hypercholesterolemia is comparable to
Harsh Bahrar1, Kim Steward2, Liesbeth van Emst1
1Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Insights
Statin treatment normalized monocyte function in patients with severe hypercholesterolemia, resolving the hyperresponsive innate immune phenotype previously observed. Neutrophil function also showed normalization, with some reduced granular protein secretion.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Genetics
Background:
- Hypercholesterolemia is a key risk factor for atherosclerotic cardiovascular disease.
- Innate immune cells like monocytes and neutrophils are implicated in atherosclerosis development.
- Previous research indicated a persistent hyperresponsive monocyte phenotype (trained immunity) in severe hypercholesterolemia, even after statin treatment.
Purpose of the Study:
- To investigate the long-term effects of 12-month statin treatment on monocyte and neutrophil phenotype in severe hypercholesterolemia.
- To compare immune cell function in treated patients with normocholesterolemic controls.
Main Methods:
- A multicentric cross-sectional study included treatment-naïve severe hypercholesterolemia patients (LDL-c > 4.9 mmol/L) after 12 months of statin therapy (n=15).
- Comparison was made with healthy normocholesterolemic controls (LDL-c < 3.5 mmol/L; n=18).
- Monocyte phenotype, PBMC cytokine production, H3K4me3 on the TNFA promotor, and neutrophil phenotype/function were assessed.
Main Results:
- Statin treatment effectively lowered LDL-c from 5.8 to 2.7 mmol/L.
- Monocyte cytokine production capacity and H3K4me3 expression on the TNFA promotor were similar to controls.
- Neutrophil phenotype (CD11b, CD66b, CD62L expression) was similar, but granular protein secretion was reduced compared to controls.
Conclusions:
- Twelve months of statin therapy normalized the previously observed hyperresponsive monocyte phenotype in severe hypercholesterolemia.
- The innate immune memory (trained immunity) associated with high LDL-c appears reversible with sustained statin treatment.
- While neutrophil phenotype normalized, reduced granular protein secretion warrants further investigation.
Background And Aims:
Hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease. Innate immune cells, including monocytes and neutrophils, play important roles in the pathophysiology of atherosclerosis. We previously reported that monocytes from patients with severely elevated low-density lipoprotein (LDL) cholesterol (LDL-c > 4.9 mmol/l) have a hyperresponsive phenotype, which persists even after three months statin treatment. This long-term hyperresponsive innate immune phenotype is termed trained immunity (innate immune memory), and is mediated by persistent enrichment of activating histone modifications leading to higher chromatin accessibility. In this study we investigated the monocyte and neutrophil phenotype of patients with severe hypercholesterolemia treated for 12 months with statins, compared to normocholesterolemic controls.
Methods:
In a multicentric cross-sectional study, treatment-naïve patients with severe hypercholesterolemia (defined as LDL-cholesterol >4.9 mmol/L) requiring statin treatment were included. Blood was drawn after 12 months of lipid lowering therapy with statins (n = 15) and compared to healthy normocholesterolemic controls (LDL-c<3.5 mmol/l; n = 18).We assessed monocyte phenotype with flow cytometry, cytokine production capacity of PBMCs, and H3K4me3 expression on the TNFA promotor. In addition, we assessed the neutrophil phenotype and function.
Results:
Treatment lowered LDL-c from 5.8 to 2.7 mmol/L. PBMC cytokine production capacity, as well as the expression of H3K4me3 histone mark on the TNFA promotor did not differ from the controls (LDL-c 2.6 mmol/L). Although neutrophil CD11b, CD66b, and CD62L expression was the same, production of several granular proteins was lower in patients.
Conclusions:
Previous studies reported hyperresponsive monocytes in treatment-naïve patients with LDL-c > 4.9 mmol/l. We now demonstrate that in an independent cohort of patients with LDL-c > 4.9 who are treated for 12 months with lipid-lowering drugs, the monocyte phenotype and function was similar to that of normocholesterolemic controls. In addition, neutrophils phenotype was similar, while the secretion of several granular proteins was lower in the patients.
More Related Videos
Related Concept Videos
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...
01:38Inflammation
01:25Blood Studies for Cardiovascular System III: Serum Lipid Profile
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
01:26Atherosclerosis III: Management
01:30Atherosclerosis I: Introduction