The role of pericytes in angiogenesis

Department of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy.
The International journal of developmental biology (Impact Factor: 1.9). 01/2011; 55(3):261-8. DOI: 10.1387/ijdb.103167dr
Source: PubMed


Pericytes are branched cells embedded within the basement membrane of capillaries and post-capillary venules. They provide an incomplete investment to endothelial cells, thus reinforcing vascular structure and regulating microvascular blood flow. Pericytes exert an important role on endothelial cell proliferation, migration and stabilization. Endothelial cells, in turn, stimulate expansion and activation of the pericyte precursor cell population. The balance between the number of endothelial cells and pericytes is highly controlled by a series of signaling pathway mechanisms operating in an autocrine and/or paracrine manner. In this review, we will first examine the molecular aspects of the pericyte activating factors secreted by endothelial cells, such as platelet derived growth factor B (PDGF-B), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β) and angiopoietins (Angs), as well as signaling pathways involving Notch and ephrins. We will then consider the complex and multivarious contribution of pericytes to the different aspects of angiogenesis with particular emphasis on the potential role of these cells as targets in tumor therapy.

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    • "Pericytes are branched cells embedded within the basement membrane of capillaries and post-capillary venules [12]. They provide an incomplete coating to ECs, thus reinforcing vascular structure and regulating microvascular blood flow [11]. "
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    ABSTRACT: Angiogenesis is sustained by classical and non-classical proangiogenic factors (PFs) acting in tumor microenvironment and these factors are also potential targets of antiangiogenic therapies. All PFs induce the overexpression of several signaling pathways that lead to migration and proliferation of endothelial cells contributing to tumor angiogenesis and survival of cancer cells. In this review, we have analysed each PF with its specific receptor/s and we have summarized the available antiangiogenic drugs (e.g. monoclonal antibodies) targeting these PFs, some of these agents have already been approved, others are currently in development for the treatment of several human malignancies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Cancer letters 07/2015; DOI:10.1016/j.canlet.2015.07.028 · 5.62 Impact Factor
    • "Mature blood vessels consist of an endothelium composed of quiescent endothelial cells sitting on a vascular basement membrane (BM). The vessel is supported by pericytes which use weblike extremities to envelope the vessel [19] and an outer layer of vascular smooth muscle (VSM) and adventitial fibroblasts [20]. The maintenance of vessel growth and expansion within the bronchial vasculature are regulated by an array of cell types ranging from endothelial progenitor cells (EPCs), to the mural cells which support the vessels, and airway structural cells such as ASM cells and fibroblasts, as summarised in Fig. 2. 2.3.1. "
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    ABSTRACT: In chronic lung disorders such as in asthma and chronic obstructive pulmonary disease (COPD) there is increased bronchial angiogenesis and remodelling of pulmonary vessels culminating to altered bronchial and pulmonary circulation. The involvement of residential cells such as endothelial cells, smooth muscle cells and pulmonary fibroblasts, all appear to have a crucial role in the progression of vascular inflammation and remodelling. The regulatory abnormalities, growth factors and mediators implicated in the pulmonary vascular changes of asthma and COPD subjects and potential therapeutic targets have been described in this review.
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    • "Indeed, a loss or lack of pericytes results in weaknesses in the capillaries, and has been associated with micro-aneurysms and loss of sight [4]–[5]. Pericytes are a heterogeneous population of perivascular cells located in close proximity to endothelial cells beneath a common basement membrane [2], [6]–[7]. To date, no specific pan-pericyte marker has been identified. "
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    ABSTRACT: CD248 (Endosialin) is a type 1 membrane protein involved in developmental and pathological angiogenesis through its expression on pericytes and regulation of PDGFRβ signalling. Here we explore the function of CD248 in skeletal muscle angiogenesis. Two distinct forms of capillary growth (splitting and sprouting) can be induced separately by increasing microcirculatory shear stress (chronic vasodilator treatment) or by inducing functional overload (extirpation of a synergistic muscle). We show that CD248 is present on pericytes in muscle and that CD248-/- mice have a specific defect in capillary sprouting. In contrast, splitting angiogenesis is independent of CD248 expression. Endothelial cells respond to pro-sprouting angiogenic stimulus by up-regulating gene expression for HIF1α, angiopoietin 2 and its receptor TEK, PDGF-B and its receptor PDGFRβ; this response did not occur following a pro-splitting angiogenic stimulus. In wildtype mice, defective sprouting angiogenesis could be mimicked by blocking PDGFRβ signalling using the tyrosine kinase inhibitor Imatinib mesylate. We conclude that CD248 is required for PDGFRβ-dependant capillary sprouting but not splitting angiogenesis, and identify a new role for CD248 expressed on pericytes in the early stages of physiological angiogenesis during muscle remodelling.
    PLoS ONE 09/2014; 9(9):e107146. DOI:10.1371/journal.pone.0107146 · 3.23 Impact Factor
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