Role of the Cytoskeleton in Formation and Maintenance of Angiogenic Sprouts

Abstract

Angiogenesis is the formation of new blood vessels from pre-existing structures, and is a key step in tissue and organ development, wound healing and pathological events. Changes in cell shape orchestrated by the cytoskeleton are integral to accomplishing the various steps of angiogenesis, and an intact cytoskeleton is also critical for maintaining newly formed structures. This review focuses on how the 3 main cytoskeletal elements – microfilaments, microtubules, and intermediate filaments – regulate the formation and maintenance of angiogenic sprouts. Multiple classes of compounds target microtubules and microfilaments, revealing much about the role of actin and tubulin and their associated molecules in angiogenic sprout formation and maintenance. In contrast, intermediate filaments are much less studied, yet intriguing evidence suggests a vital, but unresolved, role in angiogenic sprouting. This review discusses evidence for regulatory molecules and pharmacological compounds that affect actin, microtubule and intermediate filament dynamics to alter various steps of angiogenesis, including endothelial sprout formation and maintenance.

Tips, Stalks, Tubes: Notch-Mediated Cell Fate Determination and Mechanisms of Tubulogenesis during Angiogenesis

“…Instead the authors propose that F-actin is recruited in a VE-cadherin-dependent manner to the luminal surface to establish polarity. F-actin is apically localized during cat corneal endothelial wound healing (Petroll et al 1995), and altering F-actin results in erratic vascular lumenization (Cattelino et al 2003), which supports the role of cytoskeletal reorganization in forming and maintaining angiogenic sprouts (Bayless and Johnson 2011). Proper microtubule architecture is also necessary for maintaining capillary-like tubes in vitro (Connolly et al 2002;Bayless and Davis 2004).…”

Filopodia are dispensable for endothelial tip cell guidance

“…Filamentous actin (F-actin) can assemble into distinct cellular structures, such as filopodia and lamellipodia, that confer the capacity to migrate (Chhabra and Higgs, 2007). In addition, the actin cytoskeleton provides anchorage to the extracellular matrix through focal adhesions and to neighbouring cells through adherens junctions (Bayless and Johnson, 2011). The cytoskeleton therefore senses both external forces applied to the cell and the mechanical properties of the cell's environment (Pollard and Cooper, 2009).…”

Endothelial SRF/MRTF ablation causes vascular disease phenotypes in murine retinae

“…Stalk cells form the sprout base and maintain a continuous, lumenized connection to the existing vessel network (11). EC sprouting is highly dynamic and requires rapid rearrangements of the actin cytoskeleton (12). To sense VEGF gradients and other signals, tip cells continuously extend and retract filopodia and constantly compete with stalk cells for the leading position within angiogenic sprouts (13).…”