کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1995384 | 1064966 | 2009 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Inhibition of angiogenesis in vitro: A central role for β-actin dependent cytoskeletal remodeling Inhibition of angiogenesis in vitro: A central role for β-actin dependent cytoskeletal remodeling](/preview/png/1995384.png)
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 β-actin network. Specifically, the β-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, βcap73. We hypothesize that regulated over-expression of βcap73 could disrupt angiogenesis by capping β-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 βcap73 (Ad-βcap73), 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-βcap73 inhibits cEC migration in wound healing studies. Quantitative in vitro angiogenesis assays reveal that Ad-βcap73 not only prevents endothelial cells from forming capillary-like networks, but also induces the collapse of preformed endothelial tubes. In testing whether Ad-βcap73 impairs angiogenic events by inducing anoikis/apoptosis, we demonstrate that βcap73 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 βcap73 over-expression may represent an innovative therapeutic approach capable of abrogating pathologic angiogenesis.
Journal: Microvascular Research - Volume 77, Issue 3, May 2009, Pages 281–288