Bone marrow angiotensin AT receptor deficiency aggravates atherosclerosis development by eliminating macrophage liver X receptor-mediated anti-atherogenic actions
Background: Bone marrow (BM) Angiotensin II (Ang II) type 1 (AT 1 ) receptor plays a crucial role in atherosclerosis development; however, the effect of BM Ang II type 2 (AT 2 ) receptor on atherogenesis remains undefined. Methods and results: We generated BM chimera apoE-deficient ( apoE −/− ) mice...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publications
2015-12-01
|
| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.1177/1470320314561138 |
| _version_ | 1797282276131733504 |
|---|---|
| author | Taku Kato Hiroyuki Kawahito Sou Kishida Daisuke Irie Noriyuki Wakana Masakazu Kikai Hiroki Takata Takehiro Ogata Tomomi Ueyama Satoaki Matoba Hiroyuki Yamada |
| author_facet | Taku Kato Hiroyuki Kawahito Sou Kishida Daisuke Irie Noriyuki Wakana Masakazu Kikai Hiroki Takata Takehiro Ogata Tomomi Ueyama Satoaki Matoba Hiroyuki Yamada |
| author_sort | Taku Kato |
| collection | DOAJ |
| description | Background: Bone marrow (BM) Angiotensin II (Ang II) type 1 (AT 1 ) receptor plays a crucial role in atherosclerosis development; however, the effect of BM Ang II type 2 (AT 2 ) receptor on atherogenesis remains undefined. Methods and results: We generated BM chimera apoE-deficient ( apoE −/− ) mice whose BM cells were repopulated with AT 2 -deficient ( Agtr2 −/− ) or wild-type ( Agtr2 +/+ ) cells. After 2 months of a high-cholesterol diet, the atherosclerotic lesion area was significantly increased in the apoE −/− /BM-Agtr2 −/− mice compared with the apoE −/− /BM-Agtr2 +/+ mice (51%, P < 0.05), accompanied by an augmented accumulation of lesion macrophages. Although phenotypic polarization in BM-derived macrophages and lipopolysaccharide-induced expression of proinflammatory cytokines in thioglycollate-induced peritoneal macrophages (TGPMs) were not affected by AT 2 -deficiency, mRNA and protein expression levels of macrophage liver X receptor β (LXRβ) were significantly decreased in Agtr2 −/− TGPMs compared with Agtr2 +/+ TGPMs. Anti-inflammatory effects of LXR agonist (GW3965) were markedly inhibited in Agtr2 −/− TGPMs. Furthermore, the expression levels of ATP-binding cassette transporter ABCA1 and CCR7 were much lower in Agtr2 −/− TGPMs than Agtr2 +/+ TGPMs, accompanied by a significantly reduced cholesterol efflux. Conclusions: Our findings demonstrate that BM-AT 2 deficiency aggravates atherosclerosis, at least in part, by eliminating the anti-atherogenic properties of macrophages elicited by LXRβ activation. |
| first_indexed | 2024-03-07T17:10:30Z |
| format | Article |
| id | doaj.art-2bfd06508c2c430da38526d3eef5e0b8 |
| institution | Directory Open Access Journal |
| issn | 1470-3203 1752-8976 |
| language | English |
| last_indexed | 2024-03-07T17:10:30Z |
| publishDate | 2015-12-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-2bfd06508c2c430da38526d3eef5e0b82024-03-03T01:14:31ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32031752-89762015-12-011610.1177/1470320314561138Bone marrow angiotensin AT receptor deficiency aggravates atherosclerosis development by eliminating macrophage liver X receptor-mediated anti-atherogenic actionsTaku KatoHiroyuki KawahitoSou KishidaDaisuke IrieNoriyuki WakanaMasakazu KikaiHiroki TakataTakehiro OgataTomomi UeyamaSatoaki MatobaHiroyuki YamadaBackground: Bone marrow (BM) Angiotensin II (Ang II) type 1 (AT 1 ) receptor plays a crucial role in atherosclerosis development; however, the effect of BM Ang II type 2 (AT 2 ) receptor on atherogenesis remains undefined. Methods and results: We generated BM chimera apoE-deficient ( apoE −/− ) mice whose BM cells were repopulated with AT 2 -deficient ( Agtr2 −/− ) or wild-type ( Agtr2 +/+ ) cells. After 2 months of a high-cholesterol diet, the atherosclerotic lesion area was significantly increased in the apoE −/− /BM-Agtr2 −/− mice compared with the apoE −/− /BM-Agtr2 +/+ mice (51%, P < 0.05), accompanied by an augmented accumulation of lesion macrophages. Although phenotypic polarization in BM-derived macrophages and lipopolysaccharide-induced expression of proinflammatory cytokines in thioglycollate-induced peritoneal macrophages (TGPMs) were not affected by AT 2 -deficiency, mRNA and protein expression levels of macrophage liver X receptor β (LXRβ) were significantly decreased in Agtr2 −/− TGPMs compared with Agtr2 +/+ TGPMs. Anti-inflammatory effects of LXR agonist (GW3965) were markedly inhibited in Agtr2 −/− TGPMs. Furthermore, the expression levels of ATP-binding cassette transporter ABCA1 and CCR7 were much lower in Agtr2 −/− TGPMs than Agtr2 +/+ TGPMs, accompanied by a significantly reduced cholesterol efflux. Conclusions: Our findings demonstrate that BM-AT 2 deficiency aggravates atherosclerosis, at least in part, by eliminating the anti-atherogenic properties of macrophages elicited by LXRβ activation.https://doi.org/10.1177/1470320314561138 |
| spellingShingle | Taku Kato Hiroyuki Kawahito Sou Kishida Daisuke Irie Noriyuki Wakana Masakazu Kikai Hiroki Takata Takehiro Ogata Tomomi Ueyama Satoaki Matoba Hiroyuki Yamada Bone marrow angiotensin AT receptor deficiency aggravates atherosclerosis development by eliminating macrophage liver X receptor-mediated anti-atherogenic actions Journal of the Renin-Angiotensin-Aldosterone System |
| title | Bone marrow angiotensin AT receptor deficiency aggravates atherosclerosis development by eliminating macrophage liver X receptor-mediated anti-atherogenic actions |
| title_full | Bone marrow angiotensin AT receptor deficiency aggravates atherosclerosis development by eliminating macrophage liver X receptor-mediated anti-atherogenic actions |
| title_fullStr | Bone marrow angiotensin AT receptor deficiency aggravates atherosclerosis development by eliminating macrophage liver X receptor-mediated anti-atherogenic actions |
| title_full_unstemmed | Bone marrow angiotensin AT receptor deficiency aggravates atherosclerosis development by eliminating macrophage liver X receptor-mediated anti-atherogenic actions |
| title_short | Bone marrow angiotensin AT receptor deficiency aggravates atherosclerosis development by eliminating macrophage liver X receptor-mediated anti-atherogenic actions |
| title_sort | bone marrow angiotensin at receptor deficiency aggravates atherosclerosis development by eliminating macrophage liver x receptor mediated anti atherogenic actions |
| url | https://doi.org/10.1177/1470320314561138 |
| work_keys_str_mv | AT takukato bonemarrowangiotensinatreceptordeficiencyaggravatesatherosclerosisdevelopmentbyeliminatingmacrophageliverxreceptormediatedantiatherogenicactions AT hiroyukikawahito bonemarrowangiotensinatreceptordeficiencyaggravatesatherosclerosisdevelopmentbyeliminatingmacrophageliverxreceptormediatedantiatherogenicactions AT soukishida bonemarrowangiotensinatreceptordeficiencyaggravatesatherosclerosisdevelopmentbyeliminatingmacrophageliverxreceptormediatedantiatherogenicactions AT daisukeirie bonemarrowangiotensinatreceptordeficiencyaggravatesatherosclerosisdevelopmentbyeliminatingmacrophageliverxreceptormediatedantiatherogenicactions AT noriyukiwakana bonemarrowangiotensinatreceptordeficiencyaggravatesatherosclerosisdevelopmentbyeliminatingmacrophageliverxreceptormediatedantiatherogenicactions AT masakazukikai bonemarrowangiotensinatreceptordeficiencyaggravatesatherosclerosisdevelopmentbyeliminatingmacrophageliverxreceptormediatedantiatherogenicactions AT hirokitakata bonemarrowangiotensinatreceptordeficiencyaggravatesatherosclerosisdevelopmentbyeliminatingmacrophageliverxreceptormediatedantiatherogenicactions AT takehiroogata bonemarrowangiotensinatreceptordeficiencyaggravatesatherosclerosisdevelopmentbyeliminatingmacrophageliverxreceptormediatedantiatherogenicactions AT tomomiueyama bonemarrowangiotensinatreceptordeficiencyaggravatesatherosclerosisdevelopmentbyeliminatingmacrophageliverxreceptormediatedantiatherogenicactions AT satoakimatoba bonemarrowangiotensinatreceptordeficiencyaggravatesatherosclerosisdevelopmentbyeliminatingmacrophageliverxreceptormediatedantiatherogenicactions AT hiroyukiyamada bonemarrowangiotensinatreceptordeficiencyaggravatesatherosclerosisdevelopmentbyeliminatingmacrophageliverxreceptormediatedantiatherogenicactions |