Remnant Cholesterol Elicits Arterial Wall Inflammation and a Multilevel Cellular Immune Response in Humans
| Autor: | Carlijn Kuijk, Lotte C.A. Stiekema, Hein J. Verberne, Merijn Bos, Anne Langsted, Erik S.G. Stroes, Børge G. Nordestgaard, Sophie J. Bernelot Moens, Simone L. Verweij, Siroon Bekkering, Jeffrey Kroon, Johan G. Schnitzler, Carlijn Voermans |
|---|---|
| Přispěvatelé: | Graduate School, Landsteiner Laboratory, Nuclear Medicine, ACS - Amsterdam Cardiovascular Sciences, Radiology and Nuclear Medicine, Vascular Medicine, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, AII - Inflammatory diseases, AII - Amsterdam institute for Infection and Immunity, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Integrins Pathology Familial dysbetalipoproteinemia Denmark lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] 030204 cardiovascular system & hematology Systemic inflammation Monocytes chemistry.chemical_compound 0302 clinical medicine Positron Emission Tomography Computed Tomography Hyperlipoproteinemia Type III Leukocytosis Cells Cultured Immunity Cellular Arteries Middle Aged 3. Good health Cholesterol Phenotype medicine.anatomical_structure Female medicine.symptom Cardiology and Cardiovascular Medicine Signal Transduction medicine.medical_specialty Lipoproteins Bone Marrow Cells Inflammation Biology 03 medical and health sciences All institutes and research themes of the Radboud University Medical Center Monocytosis Fluorodeoxyglucose F18 medicine Humans Triglycerides Aged Arteritis Monocyte Hematopoietic Stem Cells medicine.disease 030104 developmental biology chemistry Case-Control Studies Bone marrow Radiopharmaceuticals |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology, 37, 5, pp. 969 Arteriosclerosis, Thrombosis, and Vascular Biology, 37, 969 Arteriosclerosis, thrombosis, and vascular biology, 37(5), 969-975. Lippincott Williams and Wilkins Arteriosclerosis, Thrombosis, and Vascular Biology |
| ISSN: | 1079-5642 |
| Popis: | Objective— Mendelian randomization studies revealed a causal role for remnant cholesterol in cardiovascular disease. Remnant particles accumulate in the arterial wall, potentially propagating local and systemic inflammation. We evaluated the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD). Approach and Results— Arterial wall inflammation and bone marrow activity were measured using 18 F-FDG PET/CT. Monocyte phenotype was assessed with flow cytometry. The correlation between remnant levels and hematopoietic activity was validated in the CGPS (Copenhagen General Population Study). We found a 1.2-fold increase of 18 F-FDG uptake in the arterial wall in patients with FD (n=17, age 60±8 years, remnant cholesterol: 3.26 [2.07–5.71]) compared with controls (n=17, age 61±8 years, remnant cholesterol 0.29 [0.27–0.40]; P P =0.001, with an increase in lipid droplets per monocyte), and a higher expression of surface integrins (CD11b, CD11c, and CD18). Patients with FD also exhibited monocytosis and leukocytosis, accompanied by a 1.2-fold increase of 18 F-FDG uptake in bone marrow. In addition, we found a strong correlation between remnant levels and leukocyte counts in the CGPS (n=103 953, P for trend 5×10–276). In vitro experiments substantiated that remnant cholesterol accumulates in human hematopoietic stem and progenitor cells coinciding with myeloid skewing. Conclusions— Patients with FD have increased arterial wall and cellular inflammation. These findings imply an important inflammatory component to the atherogenicity of remnant cholesterol, contributing to the increased cardiovascular disease risk in patients with FD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|