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Journal of Cell Science Mar 2021Pericytes are mural cells of the microvasculature, recognized by their thin processes and protruding cell body. Pericytes wrap around endothelial cells and play a... (Review)
Review
Pericytes are mural cells of the microvasculature, recognized by their thin processes and protruding cell body. Pericytes wrap around endothelial cells and play a central role in regulating various endothelial functions, including angiogenesis and inflammation. They also serve as a vascular support and regulate blood flow by contraction. Prior reviews have examined pericyte biological functions and biochemical signaling pathways. In this Review, we focus on the role of mechanics and mechanobiology in regulating pericyte function. After an overview of the morphology and structure of pericytes, we describe their interactions with both the basement membrane and endothelial cells. We then turn our attention to biophysical considerations, and describe contractile forces generated by pericytes, mechanical forces exerted on pericytes, and pericyte responses to these forces. Finally, we discuss 2D and 3D engineered models for studying pericyte mechano-responsiveness and underscore the need for more evolved models that provide improved understanding of pericyte function and dysfunction.
Topics: Biophysics; Endothelial Cells; Humans; Microvessels; Neovascularization, Pathologic; Pericytes
PubMed: 33753399
DOI: 10.1242/jcs.240226 -
Neuron Dec 2023Investigations of memory mechanisms have been, thus far, neuron centric, despite the brain comprising diverse cell types. Using rats and mice, we assessed the...
Investigations of memory mechanisms have been, thus far, neuron centric, despite the brain comprising diverse cell types. Using rats and mice, we assessed the cell-type-specific contribution of hippocampal insulin-like growth factor 2 (IGF2), a polypeptide regulated by learning and required for long-term memory formation. The highest level of hippocampal IGF2 was detected in pericytes, the multi-functional mural cells of the microvessels that regulate blood flow, vessel formation, the blood-brain barrier, and immune cell entry into the central nervous system. Learning significantly increased pericytic Igf2 expression in the hippocampus, particularly in the highly vascularized stratum lacunosum moleculare and stratum moleculare layers of the dentate gyrus. Igf2 increases required neuronal activity. Regulated hippocampal Igf2 knockout in pericytes, but not in fibroblasts or neurons, impaired long-term memories and blunted the learning-dependent increase of neuronal immediate early genes (IEGs). Thus, neuronal activity-driven signaling from pericytes to neurons via IGF2 is essential for long-term memory.
Topics: Animals; Mice; Rats; Hippocampus; Memory, Long-Term; Neurons; Pericytes; Signal Transduction
PubMed: 37788670
DOI: 10.1016/j.neuron.2023.08.030 -
The Journal of Clinical Investigation May 2022Pericyte-mediated capillary constriction decreases cerebral blood flow in stroke after an occluded artery is unblocked. The determinants of pericyte tone are poorly...
Pericyte-mediated capillary constriction decreases cerebral blood flow in stroke after an occluded artery is unblocked. The determinants of pericyte tone are poorly understood. We show that a small rise in cytoplasmic Ca2+ concentration ([Ca2+]i) in pericytes activated chloride efflux through the Ca2+-gated anion channel TMEM16A, thus depolarizing the cell and opening voltage-gated calcium channels. This mechanism strongly amplified the pericyte [Ca2+]i rise and capillary constriction evoked by contractile agonists and ischemia. In a rodent stroke model, TMEM16A inhibition slowed the ischemia-evoked pericyte [Ca2+]i rise, capillary constriction, and pericyte death; reduced neutrophil stalling; and improved cerebrovascular reperfusion. Genetic analysis implicated altered TMEM16A expression in poor patient recovery from ischemic stroke. Thus, pericyte TMEM16A is a crucial regulator of cerebral capillary function and a potential therapeutic target for stroke and possibly other disorders of impaired microvascular flow, such as Alzheimer's disease and vascular dementia.
Topics: Calcium; Cerebrovascular Circulation; Humans; Ischemia; Pericytes; Stroke
PubMed: 35316222
DOI: 10.1172/JCI154118 -
Angiogenesis Nov 2021Pericytes play essential roles in blood-brain barrier integrity and their dysfunction is implicated in neurological disorders such as stroke although the underlying...
Pericytes play essential roles in blood-brain barrier integrity and their dysfunction is implicated in neurological disorders such as stroke although the underlying mechanisms remain unknown. Hypoxia-inducible factor-1 (HIF-1), a master regulator of injury responses, has divergent roles in different cells especially during stress scenarios. On one hand HIF-1 is neuroprotective but on the other it induces vascular permeability. Since pericytes are critical for barrier stability, we asked if pericyte HIF-1 signaling impacts barrier integrity and injury severity in a mouse model of ischemic stroke. We show that pericyte HIF-1 loss of function (LoF) diminishes ischemic damage and barrier permeability at 3 days reperfusion. HIF-1 deficiency preserved barrier integrity by reducing pericyte death thereby maintaining vessel coverage and junctional protein organization, and suppressing vascular remodeling. Importantly, considerable improvements in sensorimotor function were observed in HIF-1 LoF mice indicating that better vascular functionality post stroke improves outcome. Thus, boosting vascular integrity by inhibiting pericytic HIF-1 activation and/or increasing pericyte survival may be a lucrative option to accelerate recovery after severe brain injury.
Topics: Animals; Blood-Brain Barrier; Brain Ischemia; Hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Ischemic Stroke; Mice; Pericytes; Stroke
PubMed: 34046769
DOI: 10.1007/s10456-021-09796-4 -
Advances in Experimental Medicine and... 2019The lung has numerous roles, including gas exchange, immune surveillance, and barrier function. Being a highly vascularized organ, the lung receives dual blood supply... (Review)
Review
The lung has numerous roles, including gas exchange, immune surveillance, and barrier function. Being a highly vascularized organ, the lung receives dual blood supply from both the pulmonary and bronchial circulation. Therefore, pericytes likely play a prominent role in lung physiology given their localization in the perivascular niche. New genetic approaches have increased our understanding of the origin and the diverse functions of lung pericytes. Lung pericytes are myofibroblast progenitors, contributing to development of fibrosis in mouse models. Lung pericytes are also capable of responding to danger signals and amplify the inflammatory response through elaboration of cytokines and adhesion molecules. In this chapter, we describe the molecular, anatomical, and phenotypical characterization of lung pericytes. We further highlight their potential roles in the pathogenesis of lung diseases including pulmonary fibrosis, asthma, and pulmonary hypertension. Finally, current gaps in knowledge and areas of ongoing investigation in lung pericyte biology are also discussed.
Topics: Animals; Asthma; Humans; Hypertension, Pulmonary; Lung; Mice; Myofibroblasts; Pericytes; Pulmonary Fibrosis
PubMed: 30937862
DOI: 10.1007/978-3-030-11093-2_3 -
Advances in Experimental Medicine and... 2019Pericytes have long been known to contribute indirectly to tumour growth by regulating angiogenesis. Thus, remodelling tumour blood vessels to maintain blood supply is... (Review)
Review
Pericytes have long been known to contribute indirectly to tumour growth by regulating angiogenesis. Thus, remodelling tumour blood vessels to maintain blood supply is critical for continued tumour growth. A role for pericytes in restricting leakage of tumour cells through blood vessels has also become evident given that adequate pericyte coverage of these blood vessels is critical for maintaining vascular permeability. Interestingly, the relocation of pericytes from blood vessels to the tumour microenvironment results in the emergence of different properties in these cells that actively promote tumour growth and metastasis-functions not associated with their well-studied role in vascular stability and permeability. These form the focus of this review.
Topics: Humans; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Pericytes; Tumor Microenvironment
PubMed: 31147875
DOI: 10.1007/978-3-030-16908-4_5 -
Advances in Experimental Medicine and... 2018The zebrafish is an outstanding model for studying vascular biology in vivo. Pericytes and vascular smooth muscle cells can be imaged as they associate with vessels and... (Review)
Review
The zebrafish is an outstanding model for studying vascular biology in vivo. Pericytes and vascular smooth muscle cells can be imaged as they associate with vessels and provide stability and integrity to the vasculature. In zebrafish, pericytes associate with the cerebral and trunk vasculature on the second day of development, as assayed by pdgfrβ and notch3 markers. In the head, cerebral pericytes are neural crest derived, except for the pericytes of the hindbrain vasculature, which are mesoderm derived. Similar to the hindbrain, pericytes on the trunk vasculature are also mesoderm derived. Regardless of their location, pericyte development depends on a complex interaction between blood flow and signalling pathways, such as Notch, SONIC HEDGEHOG and BMP signalling, all of which positively regulate pericyte numbers.Pericyte numbers rapidly increase as development proceeds in order to stabilize both the blood-brain barrier and the vasculature and hence, prevent haemorrhage. Consequently, compromised pericyte development results in compromised vascular integrity, which then evolves into detrimental pathologies. Some of these pathologies have been modelled in zebrafish by inducing mutations in the notch3, foxc1 and foxf2 genes. These zebrafish models provide insights into the mechanisms of disease as associated with pericyte biology. Going forward, these models may be key contributors in elucidating the role of vascular mural cells in regulating vessel diameter and hence, blood flow.
Topics: Animals; Blood Vessels; Blood-Brain Barrier; Myocytes, Smooth Muscle; Pericytes; Zebrafish
PubMed: 30523588
DOI: 10.1007/978-3-030-02601-1_4 -
Advances in Experimental Medicine and... 2019Pericytes (PCs) are specialized cells located abluminal of endothelial cells (ECs) on capillaries, embedded within the same basement membrane. They are essential... (Review)
Review
Pericytes (PCs) are specialized cells located abluminal of endothelial cells (ECs) on capillaries, embedded within the same basement membrane. They are essential regulators of vascular development, remodeling, and blood-retina-barrier (BRB) tightness and are therefore important components to maintain tissue homeostasis. The perivascular localization and expression of contractile proteins suggest that PCs participate in capillary blood flow regulation and neurovascular coupling. Due to their ability to differentiate into various cell types in vitro, they are regarded as potential cells for tissue repair and therapeutic approaches in regenerative medicine. Altered function or loss of PCs is associated with a multitude of CNS diseases, including diabetic retinopathy (DR). In this chapter, we will provide a short overview of retinal vascular development, the origin of PCs, and focus on PCs in retinopathy of prematurity (ROP) and in the diabetic retina. Further, animal models to study the fate of PCs and the potential role of (retinal) PCs in regeneration and wound healing will be discussed.
Topics: Animals; Blood-Retinal Barrier; Capillaries; Diabetic Retinopathy; Humans; Pericytes; Regeneration; Retina; Retinopathy of Prematurity; Wound Healing
PubMed: 30937860
DOI: 10.1007/978-3-030-11093-2_1 -
Advances in Experimental Medicine and... 2018Besides seminal functions in angiogenesis and blood pressure regulation, microvascular pericytes possess a latent tissue regenerative potential that can be revealed in... (Review)
Review
Besides seminal functions in angiogenesis and blood pressure regulation, microvascular pericytes possess a latent tissue regenerative potential that can be revealed in culture following transition into mesenchymal stem cells. Endowed with robust osteogenic potential, pericytes and other related perivascular cells extracted from adipose tissue represent a potent and abundant cell source for refined bone tissue engineering and improved cell therapies of fractures and other bone defects. The use of diverse bone formation assays in vivo, which include mouse muscle pocket osteogenesis and calvaria replenishment, rat and dog spine fusion, and rat non-union fracture healing, has confirmed the superiority of purified perivascular cells for skeletal (re)generation. As a surprising observation though, despite strong endogenous bone-forming potential, perivascular cells drive bone regeneration essentially indirectly, via recruitment by secreted factors of local osteo-progenitors.
Topics: Animals; Bone Regeneration; Cell Differentiation; Dogs; Mesenchymal Stem Cells; Mice; Osteogenesis; Pericytes; Rats; Tissue Engineering
PubMed: 30523587
DOI: 10.1007/978-3-030-02601-1_3 -
Animal Models and Experimental Medicine Aug 2023Pericytes are the main cellular components of tiny arteries and capillaries. Studies have found that pericytes can undergo morphological contraction or relaxation under... (Review)
Review
Pericytes are the main cellular components of tiny arteries and capillaries. Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines, thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation. Moreover, due to the characteristics of stem cells, pericytes can differentiate into a variety of inflammatory cell phenotypes, which then affect the immune function. Additionally, pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders. Here we review the origin, biological phenotype and function of pericytes, and discuss the potential mechanisms of pericytes in vascular microcirculation disorders, especially in pulmonary hypertension, so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.
Topics: Pericytes; Microcirculation; Endothelial Cells; Capillaries; Biology
PubMed: 37317664
DOI: 10.1002/ame2.12334