Angiotensin II injection into mice increases the uptake of oxidized LDL by their macrophages via a proteoglycan-mediated pathway.
Angiotensin II (Ang-II) has been shown to possess several atherogenic properties including its ability to induce macrophage-mediated oxidation of LDL and to form Ang-II-modified LDL which is taken up by macrophages at enhanced rate. Oxidized-LDL (Ox-LDL) is also taken up by macrophages at enhanced rate via several scavenger receptors, leading to macrophage cholesterol accumulation. In the present study we examined the effect of Ang-II on the uptake of Ox-LDL by peritoneal macrophages derived from Balb/c mice (MPM). Intraperitoneal injection of Ang-II (10(-7) M, once daily for a period of 2 days) to the mice resulted in an increased Ox-LDL uptake up to 60%, in comparison to macrophages from placebo-treated mice. Similar results were obtained when Ang-II (10(-7) M) was injected to the mice twice a week for a period of three months. This Ox-LDL uptake was Ang-II dose-dependent. The cellular uptake of acetylated-LDL (Ac-LDL), another ligand for scavenger receptors, however, was not affected by Ang-II injection to the mice. Furthermore, preincubation of the MPM with the monoclonal antibody, anti CD36, reduced macrophage uptake of Ox-LDL in Ang-II-treated mice by only 11%. Ang-II administration to mice resulted in a 60% increase in the macrophage cellular proteoglycan content. Chondroitinase treatment of MPM decreased Ox-LDL cellular uptake by 20% and by 38% in placebo-treated and Ang-II-treated cells, respectively. We thus conclude that Ang-II administration to mice enhances their macrophage Ox-LDL uptake via its stimulating effect on cellular proteoglycan content and this process can lead to foam cell formation and atherosclerosis.
Keidar
S
S
Lipid Research Laboratory, Rambam Medical Center, Technion Faculty of Medicine, Haifa, Israel. skeidar@rambam.health.gov.il
Attias
J
J
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000493:pharmacokinetics*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011509:Proteoglycans / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D008077:Lipoproteins, LDL; D011509:Proteoglycans; D014662:Vasoconstrictor Agents; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein; D000804:Angiotensin II