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Hypothalamic Neuronal Circuits Are Modulated by Insulin and Impact Metabolism 1
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Tadeu de Oliveira Diz, Sabela Casado, Rubén Nogueiras, Sulay Tovar
Another cell type that may play a role in insulin signalling in hypothalamus are the pericytes, as they are a key component of the neurovascular unit, which includes endothelial cells, astrocytes, and neurons. The pericytes are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries and venules throughout the body. In the brain, they help to maintain homeostatic and haemostatic functions, they are also implicated in the sustain and permeability of the BBB (68). Pericytes have also been found to express INSRs and reside within the hypothalamus. Intriguingly, hypothalamic neurons show increased sensitivity to insulin and enhanced Akt phosphorylation in response to pericyte-conditioned media, an effect not seen in response to other cell-conditioned media (74).
Introduction to Cancer, Conventional Therapies, and Bionano-Based Advanced Anticancer Strategies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Vascular physiology depends on the concerted interaction of several cells, including endothelial cells and pericytes. Pericytes are cells that are involved in support of vascular development and homeostasis. These cells also play a critical role in angiogenesis. This process begins with the formation of endothelial cells from pre-existing vessels, elongation of a tube, and introduction of perivascular cells [80]. Pericytes, which are found in the vascular basement membrane that is shared with endothelial cells, detach from vessel walls and promote the migration of endothelial cells into the surrounding ECM [81, 82].
Less Common Lung and Bronchial Tumours; Bronchiolo-Alveolar Ca., Carcinoids, Hamartomas, Reticuloses, Protein Disorders, Lung Deposits and Leukaemia.
Published in Fred W Wright, Radiology of the Chest and Related Conditions, 2022
The term 'haemangiopencytoma' was introduced in 1942 by Stout and Murray to describe a vascular tumour characterised by the presence of numerous capillary blood-vessels around which are grouped masses of spindle-shaped or rounded cells believed to be pericytes. Pericytes (described by Zimmerman, 1923) are separated by a fibrous sheath from the normal endothelial cells lining the capillaries. Haemangiopericytomas consist of spindle and round shaped (?modified muscle) cells lying outside the endothelial lining of the capillaries and probably have the function of altering their calibres. The tumours contain dilated radiating vessels and a dense radiating reticulum network around the tumour cells. Their origin from pericytes and immunopathological stains helps to distinguish them from haemangioendotheliomas and other vascular tumours.
Pro- and anti-fibrotic effects of vascular endothelial growth factor in chronic kidney diseases
Published in Renal Failure, 2022
Changxiu Miao, Xiaoyu Zhu, Xuejiao Wei, Mengtuan Long, Lili Jiang, Chenhao Li, Die Jin, Yujun Du
Myofibroblasts are the major secretors of collagen, driving progressive fibrosis. Besides EMT, other sources of myofibroblasts include fibroblasts, pericytes, and bone marrow-derived cells [43]. Especially pericytes, a field of intense research, are identified as precursors for myofibroblasts. Pericytes, which are inserted into capillary endothelium, can help maintain vascular integrity. In pathological conditions, pericytes may detach from the endothelial cells and differentiate into myofibroblasts, resulting in microvascular rarefaction and kidney damage, a process known as pericyte-myofibroblast transition (PMT) [44]. Thus, PMT are also one of the major sources of myofibroblasts. In a study by Lin et al., in UUO rats, blocking VEGFR-2 signaling by circulating soluble receptor ectodomains not only attenuated PMT, but also induced marked peritubular capillaries rarefaction and fibrosis [45]. Surprisingly, the authors found that the secretion of VEGF164-mediated angiogenesis was reduced in UUO, but that of VEGF120/188 (which induces abnormal angiogenesis) was increased. It can be assumed that VEGF participates in PMT through transformation into different subtypes.
Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancer
Published in Drug Delivery, 2021
Na Wang, Qin Gao, Juan Tang, YiQing Jiang, LiShi Yang, XiangXiang Shi, Yue Chen, Yan Zhang, ShaoZhi Fu, Sheng Lin
An abnormal tumor vascular system has high permeability and tortuosity, which damages the blood supply of tumor tissues and leads to hypoxia and acidity of the tumor microenvironment. Changes in the tumor microenvironment promote tumor invasion and metastasis, whereas hypoperfusion limits the entry of therapeutic drugs into the tumor, resulting in insensitivity to chemotherapy/RT4. Pericytes are considered as mediators of angiogenesis and metastasis in tumors (Carmeliet & Jain, 2000; Meng et al., 2013; Shi et al., 2019). They typically encapsulate endothelial cells, coordinate intercellular signals, establish direct cellular contact, and support endothelial cell integrity, stability, and maturation. We used LLC to establish a subcutaneous tumor model in C57 mice and used an intra-tumor injection of ES/HA-Tyr to prove that ES/HA-Tyr has better anti-tumor effects than ES (Figure 4(A,B,D)). Fluorescence staining of tumor tissues by CD31/NG2 (Figure 5(A–C), p < .05) and immunohistochemical staining of tissues by VEGF-A (Figure 6(B,C-right), p < .05) revealed that ES/HA-Tyr can more effectively inhibit tumor blood vessel growth and promote tumor vessel normalization than ES. Through the examination of tumor hypoxia by 18FMISO (Figure 5(D,E), p < .05) and HIF-1α (Figure 6(A,C-left), p < .05), we found that ES/HA-Tyr can more effectively reduce hypoxia in tumor tissues than ES.
The potential of Slit2 as a therapeutic target for central nervous system disorders
Published in Expert Opinion on Therapeutic Targets, 2020
Prativa Sherchan, Zachary D. Travis, Jiping Tang, John H. Zhang
Pericytes are special cell types that provide structural support to capillaries and interact with endothelial cells by making direct cell-cell contacts and through paracrine signals. Pericytes play a critical role during physiological and pathological angiogenesis [61]. During initial stage of angiogenesis, pericytes detach from the endothelial cells which enables endothelial cells to migrate and proliferate into surrounding extracellular matrix giving rise to sprouting new vessels which are stabilized by the newly recruited pericytes [62]. The surface of pericytes exhibited higher levels of Robo1 and low levels of Robo4 receptors. Slit2 inhibited platelet-derived growth factor (PDGF) induced human brain vascular pericyte motility in an in vitro wound-healing assay [63]. Slit2 also inhibited PDGF-induced lamellipodia formation in the pericytes, features suggestive of a pro-migratory phenotype [63]. The pericyte chemorepellent effect of Slit2 was partially decreased but not abolished by antibodies blocking Robo1 and Robo4 receptors [63]. Additionally, pericytes were found to secrete high levels of Slit2 while negligible amounts of Slit1 and Slit3 suggesting that Slit2 secreted by pericytes may act on Robo receptors in an autocrine manner to regulate pericyte function during angiogenesis. These findings provide insights into angiogenic processes that depend not only on endothelial cells but also on pericyte migration. The effect of Slit2 on pericyte function also seems to determine angiogenic regulation by Slit2 which cannot be overlooked.