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19]][“H Inhibitor”

In summary, as judged by several markers, pericytes occur in the angiogenic sprout and are abundant in the immature vascular plexuses prior to their remodeling, at least in the developing CNS.However, as mentioned in passing above, the classical definition of a pericyte as a cell embedded in the capillary basement membrane cannot be applied in these situations.However, the diameter of the pericytedeficient vessels is abnormal, promoting the idea that one of the major roles of pericytes may be to shape a uniform capillary diameter.In the absence of pericytes, the capillary diameter varies extensively, and segments of both increased and decreased diameter are seen. At late gestation, rupturing microaneurysms appear, which may have hemodynamic causes. Pericytes may exert morphogenetic control of capillary diameter through their ability to contract.Interestingly, PDGFB itself was recently added to the list of agents regulating contraction of pericytes. Another, perhaps more likely, possibility is that pericytes control capillary diameter by regulating endothelial proliferation and differentiation.This idea has been suggested previously based on in vitro coculture experiments. Absence of pericytes also leads to defects in endothelial junction formation, and to the formation of numerous cytoplasmic folds at the luminal surface of the endothelium. This suggests that pericytes control endothelial differentiation in vivo.It is likely that the uneven capillary diameter and the folded luminal endothelial surface observed in the pericytedeficient state compromise capillary blood flow.Hence, while pericytes appear critical for vascular maturation and function, the initial patterning of the vascular networks appears to proceed relatively normally in the absence of pericytes, at least in certain locations such as the embryonic brain. The retina, however, appears to be critically dependent on pericytes also for the formation of its primary vascular plexus.Together these studies may be interpreted to suggest that pericytes have a specific and profound role in sprouting angiogenesis in the retina.This would be in line with the high abundance of pericytes in the retinal microvasculature.Another possible explanation for the extreme sensitivity of the retina to pericyte loss is that the retinal vascularization is more dependent on Vemurafenib hypoxia than most other situations of developmental angiogenesis.A lack of pericytes, with the consequences for capillary perfusion discussed above, would then be expected to have immediate impact on the state of retinal hypoxia and local VEGF expression, which in turn would be expected to abrogate normal Ciclopirox vessel patterning.Other sites, where the pericytes appear to have specific, perhaps unique, functions are the kidney glomerulus and the placenta labyrinth layer.At both these sites, the pericytes form a continuous treelike core, around which capillary loops arrange in specific highdensity tufts.The structure of these tufts is aimed to meet systemic rather than local demands, and hence their structure and functions are quite distinct relative to other capillary beds.Lack of mesangial cells and placenta pericytes has a rather specific effect on the capillary tufts.In both organs, the complex tufts are exchanged for simpler structures.In the most extreme cases the glomerular tufts are replaced by single dilated capillary loops.Most likely, this reflects a critical function for the glomerular and placenta pericytes in forming the tissue pillars involved in capillary splitting by intussusception.

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