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

Jun Ichiro Koga, Kensuke Egashira, Tetsuya Matoba, Mitsuki Kubo, Yoshiko Ihara, Masaru Iwai, Masatsugu Horiuchi, Kenji Sunagawa

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1791-1800
Number of pages10
JournalHypertension Research
Volume31
Issue number9
DOIs
Publication statusPublished - Jan 1 2008

Fingerprint

Angiotensin Type 1 Receptor
Angiotensin II
Blood Vessels
Atherosclerosis
Bone Marrow
Chemokine CCL2
Apolipoproteins E
Knockout Mice
Cell Wall
Monocytes
Vascular Cell Adhesion Molecule-1
Chemotaxis
Bone Marrow Transplantation
Bone Marrow Cells
Aorta
Reactive Oxygen Species
Macrophages
Inflammation

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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. / Koga, Jun Ichiro; Egashira, Kensuke; Matoba, Tetsuya; Kubo, Mitsuki; Ihara, Yoshiko; Iwai, Masaru; Horiuchi, Masatsugu; Sunagawa, Kenji.

In: Hypertension Research, Vol. 31, No. 9, 01.01.2008, p. 1791-1800.

Research output: Contribution to journalArticle

Koga, Jun Ichiro ; Egashira, Kensuke ; Matoba, Tetsuya ; Kubo, Mitsuki ; Ihara, Yoshiko ; Iwai, Masaru ; Horiuchi, Masatsugu ; Sunagawa, Kenji. / 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. In: Hypertension Research. 2008 ; Vol. 31, No. 9. pp. 1791-1800.
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AU - Koga, Jun Ichiro

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AU - Kubo, Mitsuki

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AU - Horiuchi, Masatsugu

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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.

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