Role of pericytes in the development of cerebral cavernous malformations

Dai, Zifeng; Li, Jingwei; Liu, Ying; Wang, Rui; Yan, Han; Xiong, Zhuo; Wu, Shi-Ting; Yang, Xi; Lu, Dongbo; Zhang, Dongdong; Li, Guofu; Wang, Yuwen; Men, Chunyang; Wei, Du; Zheng, Xiangjian; Shi, Changbin

doi:10.1016/j.isci.2022.105642

Cited by 7 publications

(3 citation statements)

References 91 publications

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“…93 Pericytes in Ccm1 knockout mice have increased expression of PDGFRβ and ECM genes, particularly that encoding fibronectin-1; human CCM lesions had abundant fibronectin deposition in pericytes. 117…”

Section: Familial Cerebral Cavernous Malformationsmentioning

confidence: 99%

What Are the Roles of Pericytes in the Neurovascular Unit and Its Disorders?

Benarroch

2023

Neurology

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Pericytes are fundamental components of the neurovascular unit (NVU). They interact with endothelial cells, basal lamina (basement membrane), and glial cells and have a critical role in maintenance of blood-brain barrier (BBB) stability, local control of capillary blood flow, angiogenesis, and immune responses. Pericytes may also function as stem cells with potential to differentiate to into smooth muscle, glial cells, or neurons. A wide range on neurologic disorders, including vascular disorders, neurodegenerative disorders such as Alzheimer disease (AD), traumatic injury, and multiple sclerosis (MS) are associated with changes in pericyte structure and function affecting the NVU. Dysfunctional pericyte signaling may be a potential biomarker of NVU pathology and provides therapeutic targets for neuroprotection. The functions of pericytes and their role in neurologic disorders have been the subject of several comprehensive reviews.1-13

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Section: Familial Cerebral Cavernous Malformationsmentioning

confidence: 99%

What Are the Roles of Pericytes in the Neurovascular Unit and Its Disorders?

Benarroch

2023

Neurology

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“…The contribution of each cell type within the lesional milieu to CCM pathogenesis remains unclear. Pericytes, microglia, astrocytes, and neurons are necessary to maintain the integrity of the blood-brain barrier (BBB) and have also been associated with leukocyte infiltration and the local inflammatory response [ 12 , 57 , 58 ]. Pericytes normally regulate vascular integrity through close physical contact with ECs as well as paracrine signaling.…”

Section: Introductionmentioning

confidence: 99%

“…Brain pericytes have also been shown to have similar functions to immune-regulating cells [ 59 ]. Recent preclinical studies on CCM lesional pericytes have identified leukocyte migration/proliferation, leukocyte cell-cell adhesion/activation, and the chemokine signaling pathway [ 57 ]. Moreover, pericytes express receptors for DAMPs and inflammatory mediators (IL-1β, IL-6, TNF-α, nitric oxide [NO], matrix metallopeptidase [MMP]-2, and MMP-9) that are associated with inflammatory responses in the brain [ 60 , 61 ].…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Mechanisms in a Neurovascular Disease: Cerebral Cavernous Malformation

Li,

Srinath,

Alcazar-Felix

et al. 2023

Brain Sciences

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Cerebral cavernous malformation (CCM) is a common cerebrovascular malformation causing intracranial hemorrhage, seizures, and focal neurologic deficits. A unique CCM lesional inflammatory microenvironment has been shown to influence the clinical course of the disease. This review addresses the inflammatory cell infiltrate in the CCM lesion and the role of a defined antigen-driven immune response in pathogenicity. We summarize immune mechanisms associated with the loss of the CCM gene and disease progression, including the potential role of immunothrombosis. We also review evidence of circulating inflammatory biomarkers associated with CCM disease and its clinical activity. We articulate future directions for this research, including the role of individual cell type contributions to the immune response in CCM, single cell transcriptomics of inflammatory cells, biomarker development, and therapeutic implications. The concepts are applicable for developing diagnostic and treatment strategies for CCM and for studying other neurovascular diseases.

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Rnf-213 Knockout Induces Pericyte Reduction and Blood-Brain Barrier Impairment in Mouse

Niu

Dai

et al. 2023

Mol Neurobiol

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Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive occlusion of the internal carotid artery and the formation of an abnormal compensatory capillary network at the base of the brain. Genomics studies identi ed Ring nger protein 213 (RNF213) as a common genetic factor that increases the susceptibility to MMD in East Asian people. However, the function of RNF213 and its roles in pathogenesis of MMD is unclear. Here, we showed that genetic knockout of Rnf213 in mice causes signi cant pericytes reduction and blood-brain barrier impairment in the cortex. These phenotypes are accompanied with microglia activation and elevated level of proin ammatory cytokines. Additionally, Rnf213 de cient mice showed reduced expression of tight junction proteins, including Occludin, Claudin-5 and ZO-1. Together, these data suggested that RNF213 might contribute to the pathogenesis of MMD through disruption of pericyte homeostasis and blood-brain barrier integrity by dysregulation of in ammatory responses and tight junction formation.

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Role of pericytes in the development of cerebral cavernous malformations

Cited by 7 publications

References 91 publications

What Are the Roles of Pericytes in the Neurovascular Unit and Its Disorders?

What Are the Roles of Pericytes in the Neurovascular Unit and Its Disorders?

Inflammatory Mechanisms in a Neurovascular Disease: Cerebral Cavernous Malformation

Rnf-213 Knockout Induces Pericyte Reduction and Blood-Brain Barrier Impairment in Mouse

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