Diversity Within Pericytes

Sims, David E.

doi:10.1046/j.1440-1681.2000.03343.x

Cited by 249 publications

(173 citation statements)

References 66 publications

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“…Pericytes and VSM cells wrap around the vascular tube and their primary role has traditionally been associated with maintaining stability and controlling hemodynamic processes in the vasculature (Cleaver and Melton 2003;Sims, 2000). In the normal brain during blood vessel formation pericytes and VSM cells are recruited by endothelial cells expressing PDGF-B, to stabilize and develop the vascular tube (Hellstrom et al, 1999;Hirschi et al, 1998).…”

Section: Perivascular Pericytes and Vascular Smooth Muscle Cells In Tmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

687

327

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High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells may be the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells such as vascular cells, microglia, peripheral immune cells, and neural precursor cells also play a vital role in controlling the course of pathology. In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact as well as signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells, which can contribute up to 30% of a brain tumor mass, play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural precursor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete. V

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Section: Perivascular Pericytes and Vascular Smooth Muscle Cells In Tmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

687

327

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“…In pericyte deficiency models of newborn mice, grave retinal vascular leakage, oedema, and haemorrhage emerged, 9 which could be possibly induced by redistribution of certain junctional proteins such as VE-cadherin and occludin. 10 Furthermore, pericyte coverage rates of the abluminal endothelial surface vary extensively among different tissues and the highest pericyte density has been described in the retina as 50%, 11 which may reflect its importance to retinal endothelial barrier.…”

Section: Introductionmentioning

confidence: 99%

Strengthening tight junctions of retinal microvascular endothelial cells by pericytes under normoxia and hypoxia involving angiopoietin-1 signal way

Wang

Hui

Guo

et al. 2007

Eye

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Purpose To determine the effects of pericytes and angiopoietin-1 on the expression of occludin and zonula occludens-1 (ZO-1) in retinal endothelial cells (ECs) under both normoxic and hypoxic conditions. Methods Rat primary retinal microvascular ECs were cultured under normoxia or hypoxia in either absence or presence of pericytes conditioned medium (PCM). PCM was pretreated with or without angiopoietin-1 neutralizing antibody. Immuofluorescent staining, Western blot and RT-PCR were used to detect the alterations of occludin and ZO-1 expression. Results Under normoxia, PCM strengthened occludin and ZO-1 immunofluorescent staining at cytomembrane as well as increased their expression at both protein and mRNA level. When pretreated with angiopoietin-1 neutralizing antibody, occludin upregulation induced by PCM was significantly blocked at protein level (62%) and mRNA level (34%). Under hypoxia, the continuity of occludin and ZO-1 staining at cell boundaries was disrupted consistent with a decrease of their protein level by 31 and 27%, respectively. Also occludin and ZO-1 mRNA level decreased by 46 and 57%, respectively. PCM was observed to partially increase expression of occludin at protein and mRNA level. Angiopoietin-1 antibody slightly inhibited (16%) PCM induced occludin mRNA increase under hypoxia. Conclusion Pericytes improved the integrity of endothelial barrier through inducing occludin and ZO-1 expression at protein and mRNA level under normoxia. Under hypoxia, pericytes could partially reverse occludin decrease. These protecting effects of pericytes on endothelial barrier were at least in part mediated by angiopoietin-1.

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“…Much less is known about these perivascular cells, as evidenced by the 115-fold difference in the number of publications on endothelial cells and pericytes, respectively (revealed by a recent search of the PUBMED database). The origin, function, and even reliable identification of pericytes have been elusive [5,7,8]. As a result, the benefits of using pericytes as an additional target for anti-angiogenic therapy are just beginning to be explored [9,10].…”

Section: Introductionmentioning

confidence: 99%

Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan

2004

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The NG2 proteoglycan is expressed by nascent pericytes during the early stages of angiogenesis. To investigate the functional role of NG2 in neovascularization, we have compared pathological retinal and corneal angiogenesis in wild type and NG2 null mice. During ischemic retinal neovascularization, ectopic vessels protruding into the vitreous occur twice as frequently in wild type retinas as in NG2 null retinas. In the NG2 knock-out retina, proliferation of both pericytes and endothelial cells is significantly reduced, and the pericyte:endothelial cell ratio falls to 0.24 from the wild type value of 0.86. Similarly, bFGF-induced angiogenesis is reduced more than four-fold in the NG2 null cornea compared to that seen in the wild type retina. Significantly, NG2 antibody is effective in reducing angiogenesis in the wild type cornea, suggesting that the proteoglycan can be an effective target for anti-angiogenic therapy. These experiments therefore demonstrate both the functional importance of NG2 in pericyte development and the feasibility of using pericytes as antiangiogenic targets. Keywords

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Diversity Within Pericytes

Cited by 249 publications

References 66 publications

The brain tumor microenvironment

The brain tumor microenvironment

Strengthening tight junctions of retinal microvascular endothelial cells by pericytes under normoxia and hypoxia involving angiopoietin-1 signal way

Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan

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