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Inhibition of angiogenesis in vitro: a central role for beta-actin dependent cytoskeletal remodeling.

ABSTRACT: Endothelial cell migration and proliferation, central steps in both physiologic and pathologic angiogenesis, require cytoskeletal-dependent remodeling, which is, in large part, achieved by the dynamic regulation of the beta-actin network. Specifically, the beta-actin network has previously been shown to be (i) enriched in regions of highly motile cytoplasm, and (ii) modulated by its isoactin-specific barbed-end capping protein, beta cap73. We hypothesize that regulated over-expression of beta cap73 could disrupt angiogenesis by capping beta-actin-filament assembly thus inhibiting the incipient cellular migration and microvascular morphogenesis that ensues. Indeed, upon infection of capillary endothelial cells (cEC) with an adenovirus encoding the full-length beta cap73 (Ad-beta cap73), there is a robust cellular rounding response that occurs concomitantly with cytoskeletal disruption, as visualized with immunofluorescence microscopy. Further, we demonstrate that over-expression of Ad-beta cap73 inhibits cEC migration in wound healing studies. Quantitative in vitro angiogenesis assays reveal that Ad-beta cap73 not only prevents endothelial cells from forming capillary-like networks, but also induces the collapse of preformed endothelial tubes. In testing whether Ad-beta cap73 impairs angiogenic events by inducing anoikis/apoptosis, we demonstrate that beta cap73 infection activates a caspase-3-mediated cell death response as observed by quantitative Western blotting and immunofluorescence analyses. Altogether, these findings suggest that endothelial-specific targeting and beta cap73 over-expression may represent an innovative therapeutic approach capable of abrogating pathologic angiogenesis.

SUBMITTER: Durham JT

PROVIDER: S-EPMC2706787 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Inhibition of angiogenesis in vitro: a central role for beta-actin dependent cytoskeletal remodeling.

Durham Jennifer T JT Herman Ira M IM

Microvascular research 20090123 3

Endothelial cell migration and proliferation, central steps in both physiologic and pathologic angiogenesis, require cytoskeletal-dependent remodeling, which is, in large part, achieved by the dynamic regulation of the beta-actin network. Specifically, the beta-actin network has previously been shown to be (i) enriched in regions of highly motile cytoplasm, and (ii) modulated by its isoactin-specific barbed-end capping protein, beta cap73. We hypothesize that regulated over-expression of beta ca ...[more]

PMID: 19323981

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Inhibition of angiogenesis in vitro: a central role for beta-actin dependent cytoskeletal remodeling.

Publications

Inhibition of angiogenesis in vitro: a central role for beta-actin dependent cytoskeletal remodeling.

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