PMID- 21030715 OWN - NLM STAT- MEDLINE DCOM- 20110120 LR - 20211020 IS - 1524-4636 (Electronic) IS - 1079-5642 (Print) IS - 1079-5642 (Linking) VI - 31 IP - 1 DP - 2011 Jan TI - Macrophage adipose triglyceride lipase deficiency attenuates atherosclerotic lesion development in low-density lipoprotein receptor knockout mice. PG - 67-73 LID - 10.1161/ATVBAHA.110.215814 [doi] AB - OBJECTIVE: The consequences of macrophage triglyceride (TG) accumulation on atherosclerosis have not been studied in detail so far. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for the initial step in TG hydrolysis. Because ATGL knockout (KO) mice exhibit massive TG accumulation in macrophages, we used ATGL KO mice to study the effects of macrophage TG accumulation on atherogenesis. METHODS AND RESULTS: Low-density lipoprotein receptor (LDLr) KO mice were transplanted with bone marrow from ATGL KO (ATGL KO-->LDLr KO) or wild-type (WT-->LDLr KO) mice and challenged with a Western-type diet for 9 weeks. Despite TG accumulation in ATGL KO macrophages, atherosclerosis in ATGL KO-->LDLr KO mice was 43% reduced associated with decreased plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage interleukin-6 concentrations. This coincided with a reduced amount of macrophages, possibly because of a 39% increase in intraplaque apoptosis and a decreased migratory capacity of ATGL KO macrophages. The reduced number of white blood cells might be due to a 36% decreased Lin(-)Sca-1(+)cKit(+) hematopoietic stem cell population. CONCLUSIONS: We conclude that the attenuation of atherogenesis in ATGL KO-->LDLr KO mice is due to decreased infiltration of less inflammatory macrophages into the arterial wall and increased macrophage apoptosis. FAU - Lammers, Bart AU - Lammers B AD - Division of Biopharmaceutics, Gorlaeus Laboratories, Einsteinweg 55, 2333CC Leiden, the Netherlands. b.lammers@lacdr.leidenuniv.nl FAU - Chandak, Prakash G AU - Chandak PG FAU - Aflaki, Elma AU - Aflaki E FAU - Van Puijvelde, Gijs H M AU - Van Puijvelde GH FAU - Radovic, Branislav AU - Radovic B FAU - Hildebrand, Reeni B AU - Hildebrand RB FAU - Meurs, Illiana AU - Meurs I FAU - Out, Ruud AU - Out R FAU - Kuiper, Johan AU - Kuiper J FAU - Van Berkel, Theo J C AU - Van Berkel TJ FAU - Kolb, Dagmar AU - Kolb D FAU - Haemmerle, Guenter AU - Haemmerle G FAU - Zechner, Rudolf AU - Zechner R FAU - Levak-Frank, Sanja AU - Levak-Frank S FAU - Van Eck, Miranda AU - Van Eck M FAU - Kratky, Dagmar AU - Kratky D LA - eng GR - F 3001/FWF_/Austrian Science Fund FWF/Austria GR - F 3002/FWF_/Austrian Science Fund FWF/Austria GR - F 3004/FWF_/Austrian Science Fund FWF/Austria GR - P 19186/FWF_/Austrian Science Fund FWF/Austria PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101028 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-6) RN - 0 (Receptors, LDL) RN - 0 (Triglycerides) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.1.1.- (Carboxylic Ester Hydrolases) RN - EC 3.1.1.3 (Lipase) RN - EC 3.1.1.3 (PNPLA2 protein, mouse) SB - IM MH - Animals MH - Apoptosis MH - Atherosclerosis/enzymology/etiology/genetics/immunology/pathology/*prevention & control MH - Bone Marrow Transplantation MH - Carboxylic Ester Hydrolases/*deficiency/genetics MH - Cells, Cultured MH - Chemokine CCL2/blood MH - Chemotaxis MH - Cholesterol/blood MH - Diet, Atherogenic MH - Disease Models, Animal MH - Female MH - Gene Expression Regulation MH - Hematopoietic Stem Cells/metabolism MH - Hydrolysis MH - Inflammation Mediators/metabolism MH - Interleukin-6/metabolism MH - Leukocyte Count MH - Lipase MH - Macrophages/*enzymology/immunology/pathology MH - Male MH - Mice MH - Mice, Knockout MH - Multipotent Stem Cells/metabolism MH - Receptors, LDL/*deficiency/genetics MH - Triglycerides/blood/*metabolism MH - Whole-Body Irradiation PMC - PMC3063945 MID - UKMS33613 OID - NLM: UKMS33613 EDAT- 2010/10/30 06:00 MHDA- 2011/01/21 06:00 PMCR- 2011/03/25 CRDT- 2010/10/30 06:00 PHST- 2010/10/30 06:00 [entrez] PHST- 2010/10/30 06:00 [pubmed] PHST- 2011/01/21 06:00 [medline] PHST- 2011/03/25 00:00 [pmc-release] AID - ATVBAHA.110.215814 [pii] AID - 10.1161/ATVBAHA.110.215814 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):67-73. doi: 10.1161/ATVBAHA.110.215814. Epub 2010 Oct 28.