Dataset Information

IQGAP1 is involved in post-ischemic neovascularization by regulating angiogenesis and macrophage infiltration.

ABSTRACT:

Background

Neovascularization is an important repair mechanism in response to ischemic injury and is dependent on inflammation, angiogenesis and reactive oxygen species (ROS). IQGAP1, an actin-binding scaffold protein, is a key regulator for actin cytoskeleton and motility. We previously demonstrated that IQGAP1 mediates vascular endothelial growth factor (VEGF)-induced ROS production and migration of cultured endothelial cells (ECs); however, its role in post-ischemic neovascularization is unknown.

Methodology/principal findings

Ischemia was induced by left femoral artery ligation, which resulted in increased IQGAP1 expression in Mac3(+) macrophages and CD31(+) capillary-like ECs in ischemic legs. Mice lacking IQGAP1 exhibited a significant reduction in the post-ischemic neovascularization as evaluated by laser Doppler blood flow, capillary density and ?-actin positive arterioles. Furthermore, IQGAP1(-/-) mice showed a decrease in macrophage infiltration and ROS production in ischemic muscles, leading to impaired muscle regeneration and increased necrosis and fibrosis. The numbers of bone marrow (BM)-derived cells in the peripheral blood were not affected in these knockout mice. BM transplantation revealed that IQGAP1 expressed in both BM-derived cells and tissue resident cells, such as ECs, is required for post-ischemic neovascularization. Moreover, thioglycollate-induced peritoneal macrophage recruitment and ROS production were inhibited in IQGAP1(-/-) mice. In vitro, IQGAP1(-/-) BM-derived macrophages showed inhibition of migration and adhesion capacity, which may explain the defective macrophage recruitment into the ischemic tissue in IQGAP1(-/-) mice.

Conclusions/significance

IQGAP1 plays a key role in post-ischemic neovascularization by regulating, not only, ECs-mediated angiogenesis but also macrophage infiltration as well as ROS production. Thus, IQGAP1 is a potential therapeutic target for inflammation- and angiogenesis-dependent ischemic cardiovascular diseases.

SUBMITTER: Urao N

PROVIDER: S-EPMC2955540 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

IQGAP1 is involved in post-ischemic neovascularization by regulating angiogenesis and macrophage infiltration.

Urao Norifumi N Razvi Masooma M Oshikawa Jin J McKinney Ronald D RD Chavda Rupal R Bahou Wadie F WF Fukai Tohru T Ushio-Fukai Masuko M

PloS one 20101015 10

<h4>Background</h4>Neovascularization is an important repair mechanism in response to ischemic injury and is dependent on inflammation, angiogenesis and reactive oxygen species (ROS). IQGAP1, an actin-binding scaffold protein, is a key regulator for actin cytoskeleton and motility. We previously demonstrated that IQGAP1 mediates vascular endothelial growth factor (VEGF)-induced ROS production and migration of cultured endothelial cells (ECs); however, its role in post-ischemic neovascularization ...[more]

PMID: 20976168

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Dataset Information

IQGAP1 is involved in post-ischemic neovascularization by regulating angiogenesis and macrophage infiltration.

Background

Methodology/principal findings

Conclusions/significance

Publications

IQGAP1 is involved in post-ischemic neovascularization by regulating angiogenesis and macrophage infiltration.

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