Impact of bone marrow ATP-binding cassette transporter A1 deficiency on atherogenesis is independent of the presence of the low-density lipoprotein receptor
| Autor: | Miranda Van Eck, Ying Zhao, Laura Calpe-Berdiel, Menno Hoekstra, Theo J.C. Van Berkel, Amber B. Ouweneel, Bart Lammers |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Lymphocyte 030204 cardiovascular system & hematology 03 medical and health sciences Mice 0302 clinical medicine Bone Marrow Internal medicine medicine polycyclic compounds Animals cardiovascular diseases Foam cell Mice Knockout biology Chemistry nutritional and metabolic diseases Atherosclerosis Transplantation Lipoproteins LDL Haematopoiesis 030104 developmental biology medicine.anatomical_structure Endocrinology Cholesterol Receptors LDL ABCA1 LDL receptor biology.protein ATP-Binding Cassette Transporters lipids (amino acids peptides and proteins) Abca1 Bone marrow Cardiology and Cardiovascular Medicine Lipoprotein ATP Binding Cassette Transporter 1 |
| Zdroj: | Atherosclerosis, 319, 79-85 |
| Popis: | BACKGROUND AND AIMS\nMETHODS\nRESULTS\nCONCLUSIONS\nThere is extensive evidence from bone marrow transplantation studies that hematopoietic ATP binding cassette A1 (Abca1) is atheroprotective in low-density lipoprotein receptor (Ldlr) deficient mice. In contrast, studies using lysosyme M promoter-driven deletion of Abca1 in Ldlr deficient mice failed to show similar effects. It was hypothesized that the discrepancy between these studies might be due to the presence of Ldlr in bone marrow-derived cells in the transplantation model. In this study, we aim to determine the contribution of Ldlr to the atheroprotective effect of hematopoietic Abca1 in the murine bone marrow transplantation model.\nWild-type, Ldlr-/-, Abca1-/-, and Abca1-/-Ldlr-/- bone marrow was transplanted into hypercholesterolemic Ldlr-/- mice.\nBone marrow Lldr deficiency did not influence the effects of Abca1 on macrophage cholesterol efflux, foam cell formation, monocytosis or plasma cholesterol. Ldlr deficiency did reduce circulating and peritoneal lymphocyte counts, albeit only in animals lacking Abca1 in bone marrow-derived cells. Importantly, the effects of Abca1 deficiency on atherosclerosis susceptibility were unaltered by the presence or absence of Ldlr. Bone marrow Ldlr deficiency did lead to marginally but consistently decreased atherosclerosis, regardless of Abca1 deficiency. Thus, Ldlr expression on bone marrow-derived cells does, to a minimal extent, influence atherosclerotic lesion development, albeit independent of Abca1.\nThis study provides novel insight into the relative impact of Ldlr and Abca1 in bone marrow-derived cells on macrophage foam cell formation and atherosclerosis development in vivo. We have shown that Ldlr and Abca1 differentially and independently influence atherosclerosis development in a murine bone marrow transplantation model of atherosclerosis. |
| Databáze: | OpenAIRE |
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