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Vascular Embryology and Angiogenesis
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In simple terms, the cardiovascular system consists of a sophisticated pump (i.e., the heart) and a remarkable array of tubes (i.e., the blood and lymphatic vessels). Arteries and arterioles (the efferent blood vessels in relation to the heart) deliver oxygen, nutrients, paracrine hormones, blood and immune cells, and many other products to the capillaries, small-caliber, thin-walled vascular tubes. These substances are then transported through the capillary wall into the extravascular tissues, where they participate in critical physiological processes. In turn, waste products are transported from the extravascular space back into the blood capillaries and returned by the venules and veins (the afferent vessels) to the heart. Alternatively, approximately 10% of the fluid returned to the heart courses via the lymphatic system to the large veins. To develop normally, the embryo requires the delivery of nutrients and removal of waste products beginning early in development, and, indeed...
Endothelial cell division in angiogenic sprouts of differing cellular architecture
Biology open, 2015
The vasculature of the zebrafish trunk is composed of tubes with different cellular architectures. Unicellular tubes form their lumen through membrane invagination and transcellular cell hollowing, whereas multicellular vessels become lumenized through a chord hollowing process. Endothelial cell proliferation is essential for the subsequent growth and maturation of the blood vessels. However, how cell division, lumen formation and cell rearrangement are coordinated during angiogenic sprouting has so far not been investigated at detailed cellular level. Reasoning that different tubular architectures may impose discrete mechanistic constraints on endothelial cell division, we analyzed and compared the sequential steps of cell division, namely mitotic rounding, cytokinesis, actin re-distribution and adherence junction formation, in different blood vessels. In particular, we characterized the interplay between cell rearrangement, mitosis and lumen dynamics within unicellular and multice...
Laboratory investigation; a journal of technical methods and pathology, 2001
Vasculogenesis, the de novo formation of new blood vessels from undifferentiated precursor cells or angioblasts, has been studied with experimental in vivo and ex vivo animal models, but its mechanism is poorly understood, particularly in humans. We used the aortic ring assay to investigate the angioforming capacity of aortic explants from 11-to 12-week-old human embryos. After being embedded in collagen gels, the aorta rings produced branching capillary-like structures formed by mesenchymal spindle cells that lined a capillary-like lumen and expressed markers of endothelial differentiation (CD31, CD34, von Willebrand factor [vWF], and fms-like tyrosine kinase-1 [Flk-1]/vascular endothelial growth factor receptor 2 [VEGFR2]). The cell linings of these structures showed ultrastructural evidence of endothelial differentiation. The neovascular proliferation occurred primarily in the outer aspects of aortic rings, thus suggesting that the new vessels mainly arose from immature endothelial precursor cells localized in the outer layer of the aortic stroma, ie, a process of vasculogenesis rather than angiogenesis. The undifferentiated mesenchymal cells (CD34ϩ/CD31Ϫ), isolated and cultured on collagen-fibronectin, differentiated into endothelial cells expressing CD31 and vWF. Furthermore, the CD34ϩ/CD31ϩ cells were capable of forming a network of capillary-like structures when cultured on Matrigel. This is the first reported study showing the ex vivo formation of human microvessels by vasculogenesis. Our findings indicate that the human embryonic aorta is a rich source of CD34ϩ/CD31Ϫ endothelial progenitor cells (angioblasts), and this information may prove valuable in studies of vascular regeneration and tissue bioengineering. (Lab Invest 2001, 81:875-885).
Intussusceptive angiogenesis and its role in vascular morphogenesis, patterning, and remodeling
Angiogenesis, 2009
New blood vessels arise initially as blood islands in the process known as vasculogenesis or as new capillary segments produced through angiogenesis. Angiogenesis itself encompasses two broad processes, namely sprouting (SA) and intussusceptive (IA) angiogenesis. Primordial capillary plexuses expand through both SA and IA, but subsequent growth and remodeling are achieved through IA. The latter process proceeds through transluminal tissue pillar formation and subsequent vascular splitting, and the direction taken by the pillars delineates IA into overt phases, namely: intussusceptive microvascular growth, intussusceptive arborization, and intussusceptive branching remodeling. Intussusceptive microvascular growth circumscribes the process of initiation of pillar formation and their subsequent expansion with the result that the capillary surface area is greatly enhanced. In contrast, intussusceptive arborization entails formation of serried pillars that remodel the disorganized vascular meshwork into the typical tree-like arrangement. Optimization of local vascular branching geometry occurs through intussusceptive branching remodeling so that the vasculature is remodeled to meet the local demand. In addition, IA is important in creation of the local organspecific angioarchitecture. While hemodynamic forces have proven direct effects on IA, with increase in blood flow resulting in initiation of pillars, the preponderant mechanisms are unclear. Molecular control of IA has so far not been unequivocally elucidated but interplay among several factors is probably involved. Future investigations are strongly encouraged to focus on interactions among angiogenic growth factors, angiopoetins, and related receptors.
Distal angiogenesis: a new concept for lung vascular morphogenesis
AJP: Lung Cellular and Molecular Physiology, 2004
Although several molecular players have been described that play a role during the early phases of lung development, it is still unknown how the vasculature develops in relation to the airways. Two opposing models describe the development of the lung vasculature: one suggests that both vasculogenesis and angiogenesis are involved, whereas the second describes vasculogenesis as the primary mechanism. Therefore, we examined the development of the murine pulmonary vasculature through a morphological analysis from the onset of lung development (9.5 dpc) until the pseudoglandular stage (13.5 dpc). We analysed fetal lungs of Tie2-LacZ transgenic mice as well as serial sections of wild type lungs stained with endothelial-specific antibodies (Flk-1, Fli-1 and PECAM-1). Embryos were processed with intact blood circulation to maintain the integrity of the vasculature, hence individual vessels could be identified with accuracy through serial section analysis.