Abstract
Angiogenesis—the sprouting and growth of new blood vessels from the existing vasculature—is an important contributor to tumor development, since it facilitates the supply of oxygen and nutrients to cancer cells. Endothelial cells are critically affected during the angiogenic process as their proliferation, motility, and morphology are modulated by pro-angiogenic and environmental factors associated with tumor tissues and cancer cells. Recent in vivo and in vitro studies have revealed that the gap junctions of endothelial cells also participate in the promotion of angiogenesis. Pro-angiogenic factors modulate gap junction function and connexin expression in endothelial cells, whereas endothelial connexins are involved in angiogenic tube formation and in the cell migration of endothelial cells. Several mechanisms, including gap junction function-dependent or -independent pathways, have been proposed. In particular, connexins might have the potential to regulate cell mechanics such as cell morphology, cell migration, and cellular stiffness that are dynamically changed during the angiogenic processes. Here, we review the implication for endothelial gap junctions and cellular mechanics in vascular angiogenesis.
Highlights
Vasculogenesis leads to the creation of the heart and the first primitive vascular plexus inside the embryo and its surrounding membranes, as can be observed in yolk sac circulation
Recent studies have indicated that gap junctions and Cxs in endothelial cells contribute to several important steps in angiogenesis such as sprouting, migration, tube formation, and cellular stiffness, all of which are implicated in cellular mechanics
This study has provided the first evidence that endothelial gap junction contributes to the regulation of endothelial cellular stiffness via interaction with cytoskeletal rearrangements
Summary
Vasculogenesis leads to the creation of the heart and the first primitive vascular plexus inside the embryo and its surrounding membranes, as can be observed in yolk sac circulation. Vascular endothelial cells covering the lumen of the blood vessel play a leading role in angiogenesis In response to these pro-angiogenic and environmental factors, endothelial cells initiate angiogenic processes [3,4], which can be categorized as vascular sprouting [5], cell proliferation [6], cell migration [7], tube formation [8], and vascular stabilization [9]. Recent studies have indicated that gap junctions and Cxs in endothelial cells contribute to several important steps in angiogenesis such as sprouting, migration, tube formation, and cellular stiffness, all of which are implicated in cellular mechanics. We mainly focus on gap junctions and Cxs in endothelial cells and will discuss the implications of cellular mechanics for vascular angiogenesis
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