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PMID: 18184815 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The A2b adenosine receptor protects against vascular injury.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 2 ·2008-01-15 ·Pages 792-6

Yang D, Koupenova M, McCrann DJ, Kopeikina KJ, Kagan HM, Schreiber BM, Ravid K

Abstract

The A2b adenosine receptor (A2bAR) is highly abundant in bone marrow macrophages and vascular smooth muscle cells (VSMC). To examine the functional significance of this receptor expression, we applied a femoral artery injury model to A2bAR knockout (KO) mice and showed that the A2bAR prevents vascular lesion formation in an injury model that resembles human restenosis after angioplasty. While considering related mechanisms, we noted higher levels of TNF-alpha, an up-regulator of CXCR4, and of VSMC proliferation in the injured KO mice. In accordance, CXCR4, which is known to attract progenitor cells during tissue regeneration, is up-regulated in lesions of the KO mice. In addition, aortic smooth muscle cells derived from A2bAR KO mice display greater proliferation in comparison with controls. Bone marrow transplantation experiments indicated that the majority of the signal for lesion formation in the null mice originates from bone marrow cells. Thus, this study highlights the significance of the A2bAR in regulating CXCR4 expression in vivo and in protecting against vascular lesion formation.

MeSH Terms
Animals Aorta/metabolism Bone Marrow Cells/metabolism Bone Marrow Transplantation Cell Cycle Cell Proliferation Gene Expression Regulation Inflammation Mice Mice, Inbred C57BL Mice, Knockout Muscle, Smooth, Vascular/cytology,injuries,metabolism,pathology Receptor, Adenosine A2B/metabolism,physiology Receptors, CXCR4/metabolism Tumor Necrosis Factor-alpha/metabolism
Chemicals
CXCR4 protein, mouse Receptor, Adenosine A2B Receptors, CXCR4 Tumor Necrosis Factor-alpha
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Yang Dan
Department of Biochemistry and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.
Koupenova Milka
McCrann Donald J
Kopeikina Katherine J
Kagan Herbert M
Schreiber Barbara M
Ravid Katya
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0705563105
Published
2008-01-15
Epub
2008-00-09
Pages
792-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2206615
Subset
IM
Grants
NHLBI NIH HHS · P01 HL013262 · United States
NHLBI NIH HHS · T32 HL007969 · United States
NHLBI NIH HHS · HL13262 · United States
External Links
PubMed source DOI: 10.1073/pnas.0705563105 PMC Full Text View journal details
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