PMID- 18971558
OWN - NLM
STAT- MEDLINE
DCOM- 20090109
LR  - 20081030
IS  - 0916-9636 (Print)
IS  - 0916-9636 (Linking)
VI  - 31
IP  - 9
DP  - 2008 Sep
TI  - Essential role of angiotensin II type 1a receptors in the host vascular wall, but 
      not the bone marrow, in the pathogenesis of angiotensin II-induced 
      atherosclerosis.
PG  - 1791-800
LID - 10.1291/hypres.31.1791 [doi]
AB  - The angiotensin II (Ang II) type 1a (AT1a) receptor is expressed on multiple cell 
      types in atherosclerotic lesions, including bone marrow-derived cells and 
      vascular wall cells, and mediates inflammatory and proliferative responses. 
      Indeed, Ang II infusion accelerates atherogenesis in hyperlipidemic mice by 
      recruiting monocytes and by activating vascular wall cells. Here, we investigated 
      the relative roles of AT1a receptors in the bone marrow vs. the vascular wall in 
      Ang II-induced atherogenesis. Apolipoprotein E-knockout (ApoE(-/-)) mice with or 
      without bone marrow AT1a receptor were generated by experimental bone marrow 
      transplantation using AT1a(+/+) or AT1a(-/-) recipients. In these mice, 28-d Ang 
      II infusion induced significant atherosclerosis in the aorta, and the severity of 
      plaque formation was not affected by the absence of bone marrow AT1a receptor. We 
      then generated AT1a(-/-)ApoE(-/-) mice with or without bone marrow AT1a receptor. 
      Ang II-induced plaque formation was blunted irrespective of the presence of bone 
      marrow AT1a receptor. Host AT1a receptor deficiency was found to suppress Ang 
      II-induced reactive oxygen species production. In addition, AT1a receptor 
      deficiency also impaired monocyte chemoattractant protein-1 (MCP-1) and vascular 
      cell adhesion molecule-1 (VCAM-1) expression in the arterial wall 7 d after Ang 
      II initiation. These molecules normally initiate later macrophage-mediated 
      inflammation in the vascular wall. By contrast, AT1a receptor deficiency in the 
      bone marrow did not affect MCP-1-induced monocyte chemotaxis in vitro. In 
      conclusion, AT1a receptors in the host vascular wall, but not in the bone marrow, 
      are essential in Ang II-induced atherogenesis.
FAU - Koga, Jun-ichiro
AU  - Koga J
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan.
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Matoba, Tetsuya
AU  - Matoba T
FAU - Kubo, Mitsuki
AU  - Kubo M
FAU - Ihara, Yoshiko
AU  - Ihara Y
FAU - Iwai, Masaru
AU  - Iwai M
FAU - Horiuchi, Masatsugu
AU  - Horiuchi M
FAU - Sunagawa, Kenji
AU  - Sunagawa K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (Apolipoproteins E)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Vasoconstrictor Agents)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Apolipoproteins E/genetics
MH  - Arteries/metabolism/*pathology/physiopathology
MH  - Atherosclerosis/metabolism/*pathology/*physiopathology
MH  - Bone Marrow/metabolism/*pathology/physiopathology
MH  - Bone Marrow Transplantation
MH  - Chemokine CCL2/genetics/metabolism
MH  - Chemotaxis, Leukocyte/physiology
MH  - Chimera
MH  - Macrophages/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Oxidative Stress/drug effects/physiology
MH  - Receptor, Angiotensin, Type 1/*genetics/metabolism
MH  - Receptors, CCR2/genetics
MH  - Vasoconstrictor Agents/pharmacology
EDAT- 2008/10/31 09:00
MHDA- 2009/01/10 09:00
CRDT- 2008/10/31 09:00
PHST- 2008/10/31 09:00 [pubmed]
PHST- 2009/01/10 09:00 [medline]
PHST- 2008/10/31 09:00 [entrez]
AID - JST.JSTAGE/hypres/31.1791 [pii]
AID - 10.1291/hypres.31.1791 [doi]
PST - ppublish
SO  - Hypertens Res. 2008 Sep;31(9):1791-800. doi: 10.1291/hypres.31.1791.