RGD Reference Report - Evidence for the importance of angiotensin II type 1 receptor in ischemia-induced angiogenesis. - Rat Genome Database

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Evidence for the importance of angiotensin II type 1 receptor in ischemia-induced angiogenesis.

Authors: Sasaki, K  Murohara, T  Ikeda, H  Sugaya, T  Shimada, T  Shintani, S  Imaizumi, T 
Citation: Sasaki K, etal., J Clin Invest 2002 Mar;109(5):603-11.
RGD ID: 737810
Pubmed: PMID:11877468   (View Abstract at PubMed)
PMCID: PMC150887   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI13055   (Journal Full-text)

The role of the renin-angiotensin system (RAS) in angiogenesis is little known. Here, we show that the angiotensin II (ATII) type 1 (AT1) receptor plays an important role in ischemia-induced angiogenesis. Well-developed collateral vessels and angiogenesis were observed in wild-type (WT) mice in response to hindlimb ischemia, whereas these responses were reduced in ATII type 1a receptor knockout (AT1a(-/-)) mice. Ischemia-induced angiogenesis was also impaired in WT mice treated with the AT1 receptor blocker TCV-116. These effects were not due to reduced systemic blood pressure (SBP), because hydralazine treatment preserved angiogenesis in WT mice although it reduced SBP to a level similar to that of AT1a(-/-) mice. Infiltration of inflammatory mononuclear cells (MNCs), including macrophages and T lymphocytes, was suppressed in the ischemic tissues of AT1a(-/-) mice compared with WT mice. Double immunofluorescence staining revealed that infiltrated macrophages and T lymphocytes expressed VEGF, and the expression of VEGF and monocyte chemoattractant protein-1 was also decreased in AT1a(-/-). Finally, the impaired angiogenesis in AT1a(-/-) mice was rescued by intramuscular transplantation of MNCs obtained from WT mice, further indicating the importance of MNC infiltration in ischemia-induced angiogenesis. Thus, the ATII--AT1 receptor pathway promotes early angiogenesis by supporting inflammatory cell infiltration and angiogenic cytokine expression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
limb ischemia  ISOAgtr1a (Mus musculus)737810; 737810 RGD 
limb ischemia  IMP 737810 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Agtr1a  (angiotensin II receptor, type 1a)

Genes (Mus musculus)
Agtr1a  (angiotensin II receptor, type 1a)

Genes (Homo sapiens)
AGTR1  (angiotensin II receptor type 1)


Additional Information