Pericytes Regulate Cerebral Perfusion through VEGFR1 in Ischemic Stroke

Gong, Chang‐Xiong; Zhang, Qin; Xiong, Xiao‐Yi; Yuan, Junjie; Yang, Guoqiang; Huang, Jiacheng; Liu, Juan; Duan, Chun‐Mei; Rui-Xu,; Qiu, Zhongming; Meng, Ziqi; Zhou, Kai; Wang, Faxiang; Zhao, Chenhao; Li, Fangfei; Yang, Qingwu

doi:10.1007/s10571-021-01071-w

Cited by 11 publications

(8 citation statements)

References 42 publications

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“…Pericytes are important regulators of angiogenesis [ 144 , 155 ] and may contribute to the differential response between the proangiogenic response in the nonfibrotic region of the lungs and vessel rarefaction in the fibrotic region of the lungs. Pericytes express VEGF receptors, which can stabilize vascular integrity and promote endothelial tube formation in the brain [ 140 , 156 ]. In contrast, findings from Yuan et al illustrate that pericyte dysfunction following CH contributes to the loss of microvessels in the lung [ 144 ].…”

Section: Vascular Pericytes In Pulmonary Fibrosismentioning

confidence: 99%

Role of Sensory Nerves in Pulmonary Fibrosis

Norton

2024

IJMS

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Pulmonary fibrosis results from the deposition and proliferation of extracellular matrix components in the lungs. Despite being an airway disorder, pulmonary fibrosis also has notable effects on the pulmonary vasculature, with the development and severity of pulmonary hypertension tied closely to patient mortality. Furthermore, the anatomical proximity of blood vessels, the alveolar epithelium, lymphatic tissue, and airway spaces highlights the need to identify shared pathogenic mechanisms and pleiotropic signaling across various cell types. Sensory nerves and their transmitters have a variety of effects on the various cell types within the lungs; however, their effects on many cell types and functions during pulmonary fibrosis have not yet been investigated. This review highlights the importance of gaining a new understanding of sensory nerve function in the context of pulmonary fibrosis as a potential tool to limit airway and vascular dysfunction.

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Section: Vascular Pericytes In Pulmonary Fibrosismentioning

confidence: 99%

Role of Sensory Nerves in Pulmonary Fibrosis

Norton

2024

IJMS

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“…Pericyte-derived VEGFR1 has been shown to have a crucial role in cerebrovascular formation and maintenance by stabilising brain vascular integrity and promoting pericyte coverage. Through paracrine VEGFR1 signalling, pericytes regulate brain endothelial tube formation, and intracellular VEGFR1-mediated signalling is required for pericyte migration and regulated Akt signalling in pericytes ( Gong et al, 2022 ). An in vivo model of cancer-associated retinopathy as well as an in vitro co-culture model of the blood brain barrier found that VEGFR1 induces pericyte ablation causing increased retinal vascular permeability ( Cao et al, 2010 ; Salmeri et al, 2013 ).…”

Section: Pericyte Responses To the Microenvironmentmentioning

confidence: 99%

Pericytes: The lung-forgotten cell type

Garrison

Bignold

et al. 2023

Front. Physiol.

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Pericytes are a heterogeneous population of mesenchymal cells located on the abluminal surface of microvessels, where they provide structural and biochemical support. Pericytes have been implicated in numerous lung diseases including pulmonary arterial hypertension (PAH) and allergic asthma due to their ability to differentiate into scar-forming myofibroblasts, leading to collagen deposition and matrix remodelling and thus driving tissue fibrosis. Pericyte-extracellular matrix interactions as well as other biochemical cues play crucial roles in these processes. In this review, we give an overview of lung pericytes, the key pro-fibrotic mediators they interact with, and detail recent advances in preclinical studies on how pericytes are disrupted and contribute to lung diseases including PAH, allergic asthma, and chronic obstructive pulmonary disease (COPD). Several recent studies using mouse models of PAH have demonstrated that pericytes contribute to these pathological events; efforts are currently underway to mitigate pericyte dysfunction in PAH by targeting the TGF-β, CXCR7, and CXCR4 signalling pathways. In allergic asthma, the dissociation of pericytes from the endothelium of blood vessels and their migration towards inflamed areas of the airway contribute to the characteristic airway remodelling observed in allergic asthma. Although several factors have been suggested to influence this migration such as TGF-β, IL-4, IL-13, and periostin, recent evidence points to the CXCL12/CXCR4 pathway as a potential therapeutic target. Pericytes might also play an essential role in lung dysfunction in response to ageing, as they are responsive to environmental risk factors such as cigarette smoke and air pollutants, which are the main drivers of COPD. However, there is currently no direct evidence delineating the contribution of pericytes to COPD pathology. Although there is a lack of human clinical data, the recent available evidence derived from in vitro and animal-based models shows that pericytes play important roles in the initiation and maintenance of chronic lung diseases and are amenable to pharmacological interventions. Therefore, further studies in this field are required to elucidate if targeting pericytes can treat lung diseases.

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“…In this process, pericytes attach to the ECs, regulate the formation of the extracellular matrix and tight junctions between endothelial cells, and maintain the integrity of immature blood vessels ( Franco et al, 2011 ). Pericytes interact with ECs through a variety of signaling pathways to regulate angiogenesis, including the PDGF-B/PDGFR-B, angiopoietin (Ang)/Tie2, VEGF/VEGFR, Notch1, and Notch 3 signaling pathways ( Berger et al, 2005 ; Nakamura et al, 2016 ; Leligdowicz et al, 2018 ; Özen et al, 2018 ; Shibahara et al, 2020a ; Gong et al, 2021 ; Nguyen et al, 2021 ), and these pathways are summarized in Figure 2 . Finally, the tip cells anastomose with adjacent vascular buds to form a microvascular ring.…”

Section: The Role Of Pericytes In Ischemic Strokementioning

confidence: 99%

The Role of Pericytes in Ischemic Stroke: Fom Cellular Functions to Therapeutic Targets

Zhou

Guo

Zhang

et al. 2022

Front. Mol. Neurosci.

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Ischemic stroke (IS) is a cerebrovascular disease causing high rates of disability and fatality. In recent years, the concept of the neurovascular unit (NVU) has been accepted by an increasing number of researchers and is expected to become a new paradigm for exploring the pathogenesis and treatment of IS. NVUs are composed of neurons, endothelial cells, pericytes, astrocytes, microglia, and the extracellular matrix. As an important part of the NVU, pericytes provide support for other cellular components and perform a variety of functions, including participating in the maintenance of the normal physiological function of the blood–brain barrier, regulating blood flow, and playing a role in inflammation, angiogenesis, and neurogenesis. Therefore, treatment strategies targeting pericyte functions, regulating pericyte epigenetics, and transplanting pericytes warrant exploration. In this review, we describe the reactions of pericytes after IS, summarize the potential therapeutic targets and strategies targeting pericytes for IS, and provide new treatment ideas for ischemic stroke.

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Pericytes Regulate Cerebral Perfusion through VEGFR1 in Ischemic Stroke

Cited by 11 publications

References 42 publications

Role of Sensory Nerves in Pulmonary Fibrosis

Role of Sensory Nerves in Pulmonary Fibrosis

Pericytes: The lung-forgotten cell type

The Role of Pericytes in Ischemic Stroke: Fom Cellular Functions to Therapeutic Targets

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