Circulating Mononuclear Cells With a Dual, Macrophage-Fibroblast Phenotype Contribute Robustly to Hypoxia-Induced Pulmonary Adventitial Remodeling

Frid, Maria G.; Brunetti, Jacqueline A.; Burke, Danielle L.; Carpenter, Todd; Davie, Neil; Stenmark, Kurt R.

doi:10.1378/chest.128.6_suppl.583s

Cited by 19 publications

(14 citation statements)

References 3 publications

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“…It is possible that at least some of the SM-␣A ϩ cells we found in endarterectomized tissues are transdifferentiated from "injured ECs" in the intimal layer. This small percentage of ECs may originate from bone marrow-derived progenitor cells or resident vascular wall progenitor cells, which can incorporate into endothelial monolayer and differentiate into ECs (8,9). These observations support the possibility that bone marrow-derived outgrowth EPCs may be present in the endarterectomized tissue and that they may contribute to the neointimal formation in CTEPH patients.…”

Section: Discussionsupporting

confidence: 55%

“…Alvarez et al (1) showed that pulmonary resident microvascular endothelial progenitor cells (EPCs) (CD31 ϩ , CD144 ϩ , and CD45 Ϫ ) have vasculogenic activity and the potential to form de novo vessels (1). In chronic hypoxia-induced pulmonary hypertension, circulating mesenchymal precursors of a monocyte/macrophage lineage (fibrocytes) were recruited, and these cells contributed directly and substantially to the pulmonary artery adventitial remodeling (8,9,34). Hayashida et al (12) also showed bone marrow-derived cells mobilized to the hypertensive pulmonary arteries and contributed to pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension.…”

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confidence: 99%

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Identification of putative endothelial progenitor cells (CD34⁺CD133⁺Flk-1⁺) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension

Yao

Firth

Sacks

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a fibrotic thrombus persisting and obliterating the lumen of pulmonary arteries; its pathogenesis remains poorly defined. This study investigates a potential contribution for progenitor cell types in the development of vascular obliteration and remodeling in CTEPH patients. Endarterectomized tissue from patients undergoing pulmonary thromboendarterectomy was collected and examined for the structure and cellular composition. Our data show an organized fibrin network structure in unresolved thromboemboli and intimal remodeling in vascular wall tissues, characterized by smooth muscle alpha-actin (SM-alphaA)-positive cell proliferation in proximal regions (adjacent to thromboemboli) and neoangiogenesis/recanalization in distal regions (downstream from thromboemboli). Cells that are positively stained with CD34 and fetal liver kinase-1 (Flk-1) (CD34(+)Flk-1(+)) were identified in both the proximal and distal vascular tissues; a subpopulation of CD34(+)Flk-1(+)CD133(+) cells were further identified by immunostaining. Triple-positive cells are indicative of a population of putative endothelial progenitor cells or potential colony-forming units of endothelial cells. In addition, inflammatory cells (CD45(+)) and collagen-secreting cells (procollagen-1(+)) were detected in the proximal vascular wall. Some of the CD34(+) cells in CTEPH cells isolated from proximal regions were also positive for SM-alphaA. Our data indicate that putative progenitor cell types are present in the neointima of occluded vessels of CTEPH patients. It is possible that the microenvironment provided by thromboemboli may promote these putative progenitor cells to differentiate and enhance intimal remodeling.

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Section: Discussionsupporting

confidence: 55%

mentioning

confidence: 99%

Identification of putative endothelial progenitor cells (CD34⁺CD133⁺Flk-1⁺) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension

Yao

Firth

Sacks

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Monocytes and macrophages are the main effector cells contributing to local lung inflammation in the context of PH [60–62]. Recruitment of immune cells to the lungs contributes to vascular destruction and remodeling in the pathogenesis of chronic lung diseases, such as PH [63, 64]. In response to stimuli, endothelial cells overproduce chemokines such as fractalkine (CX 3 CL1) [65–70].…”

Section: Importance Of Bone Marrow-derived Cells In Ph Pathogenesismentioning

confidence: 99%

Origin and production of inflammatory perivascular macrophages in pulmonary hypertension

Florentin

Dutta

2017

Cytokine

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Myeloid cells, including monocytes and macrophages participate in steady state immune homeostasis and help mount the adaptive immune response during infection. The function and production of these cells in sterile inflammation, such as pulmonary hypertension (PH), is understudied. Emerging data indicate that pulmonary inflammation mediated by lung perivascular macrophages is a key pathogenic driver of pulmonary remodeling leading to increased right ventricular systolic pressure (RVSP). However, the origin of these macrophages in pulmonary inflammation is unknown. Inflammatory monocytes, the precursors of pathogenic macrophages, are derived from hematopoietic stem and progenitor cells (HSPC) in the bone marrow and spleen during acute and chronic inflammation. Understanding the role of these organs in monocytopoiesis, and the mechanisms of HSPC proliferation and differentiation in PH are important to discover therapeutic targets curbing inflammation. This review will summarize the current limited knowledge of the origin of lung macrophage subsets and over-production of inflammatory monocytes in PH.

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“…However, the main cell type that migrates to the pulmonary vessel wall originates from the bloodstream and the distribution is enlarged by the duration of hypoxia exposure [82,83]. This suggests that alveolar hypoxia-induced local inflammatory responses of the lungs may trigger another series of processes that aggravate pulmonary inflammation, characterized as the progressed accumulation of bloodstream leukocytes in the lung, which induces acute lung injury during acute phases of hypoxia, or pulmonary vascular remodeling under chronic hypoxia conditions.…”

Section: Low Alveolar Po2 Levels Activate Resident Lung Cells Which mentioning

confidence: 99%

Alveolar Hypoxia-Induced Pulmonary Inflammation: From Local Initiation to Secondary Promotion by Activated Systemic Inflammation

Chen¹,

Yang²,

Li³

et al. 2016

J Vasc Res

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Pulmonary hypertension (PH) is a pathological condition with high mortality and morbidity. Hypoxic PH (HPH) is a common form of PH occurring mainly due to lung disease and/or hypoxia. Most causes of HPH are associated with persistent or intermittent alveolar hypoxia, including exposure to high altitude and chronic obstructive respiratory disease. Recent evidence suggests that inflammation is a critical step for HPH initiation and development. A detailed understanding of the initiation and progression of pulmonary inflammation would help in exploring potential clinical treatments for HPH. In this review, the mechanism for alveolar hypoxia-induced local lung inflammation and its progression are discussed as follows: (1) low alveolar PO₂ levels activate resident lung cells, mainly the alveolar macrophages, which initiate pulmonary inflammation; (2) systemic inflammation is induced by alveolar hypoxia through alveolar macrophage activation; (3) monocytes are recruited into the pulmonary circulation by alveolar hypoxia-induced macrophage activation, which then contributes to the progression of pulmonary inflammation during the chronic phase of alveolar hypoxia, and (4) alveolar hypoxia-induced systemic inflammation contributes to the development of HPH. We hypothesize that a combination of alveolar hypoxia-induced local lung inflammation and the initiation of systemic inflammation (“second hit”) is essential for HPH progression.

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Circulating Mononuclear Cells With a Dual, Macrophage-Fibroblast Phenotype Contribute Robustly to Hypoxia-Induced Pulmonary Adventitial Remodeling

Cited by 19 publications

References 3 publications

Identification of putative endothelial progenitor cells (CD34⁺CD133⁺Flk-1⁺) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension

Identification of putative endothelial progenitor cells (CD34⁺CD133⁺Flk-1⁺) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension

Origin and production of inflammatory perivascular macrophages in pulmonary hypertension

Alveolar Hypoxia-Induced Pulmonary Inflammation: From Local Initiation to Secondary Promotion by Activated Systemic Inflammation

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Circulating Mononuclear Cells With a Dual, Macrophage-Fibroblast Phenotype Contribute Robustly to Hypoxia-Induced Pulmonary Adventitial Remodeling

Cited by 19 publications

References 3 publications

Identification of putative endothelial progenitor cells (CD34+CD133+Flk-1+) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension

Identification of putative endothelial progenitor cells (CD34+CD133+Flk-1+) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension

Origin and production of inflammatory perivascular macrophages in pulmonary hypertension

Alveolar Hypoxia-Induced Pulmonary Inflammation: From Local Initiation to Secondary Promotion by Activated Systemic Inflammation

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Product

Resources

About

Identification of putative endothelial progenitor cells (CD34⁺CD133⁺Flk-1⁺) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension

Identification of putative endothelial progenitor cells (CD34⁺CD133⁺Flk-1⁺) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension