title: Effect of angiotensin II type 2 receptor deletion in hematopoietic cells on brain ischemia-reperfusion injury.
abstract: The angiotensin II type 2 (AT(2)) receptor is expressed in bone marrow cells and may affect cell differentiation. We previously reported a beneficial role of the AT(2) receptor in ischemic brain damage. Here, we investigated the effect of AT(2) receptor stimulation in hematopoietic cells on ischemic brain injury using chimeric mice. Chimeric mice were generated by bone marrow transplantation into wild-type mice after irradiation. Bone marrow cells were prepared from wild-type (Agtr2(+)) or AT(2) receptor-deficient mice (Agtr2(-)). Six weeks after bone marrow transplantation, these chimeric mice were subjected to ischemia/reperfusion injury. Both Agtr2(+) and Agtr2(-) chimeric mice did not show a significant change in systolic and diastolic blood pressures, whereas body weight decreased in Agtr2(-) chimera. Twenty-four hours after ischemia/reperfusion injury, ischemic brain damage in Agtr2(-) chimera was exaggerated compared with that in Agtr2(+) chimera. Moreover, cerebral blood flow in the peripheral region before and after ischemia/reperfusion injury was decreased in Agtr2(-) chimera. The inflammatory response in the ipsilateral hemisphere was not significantly different, whereas tumor necrosis factor-α and monocyte chemoattractant protein 1 expressions tended to increase in the Agtr2(-) chimeric brain. Expression of methylmethane sulfonate 2, which has a neuroprotective effect, was lower in the brain of Agtr2(-) chimera. These results indicate that deletion of AT(2) receptor in blood cells has a harmful effect on ischemic brain injury.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Iwanami
authors.forename: Masaki
authors.initials: M
authors.lastname: Mogi
authors.forename: Kana
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Min
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakata
authors.forename: Fei
authors.initials: F
authors.lastname: Jing
authors.forename: Kousei
authors.initials: K
authors.lastname: Ohshima
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000379:methods; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D018932:Chemokine CCL2 / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044139:Receptor, Angiotensin, Type 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018183:Transplantation Chimera / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics
chemical_list: D018932:Chemokine CCL2; D044139:Receptor, Angiotensin, Type 2; D014409:Tumor Necrosis Factor-alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; C511778:Ube2v2 protein, mouse; D044763:Ubiquitin-Conjugating Enzymes; D003849:Deoxyguanosine