Phenotypic Heterogeneity of the Endothelium

Aird, William C.

doi:10.1161/01.res.0000255690.03436.ae

Cited by 972 publications

(781 citation statements)

References 194 publications

(196 reference statements)

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“…37 Recent reviews indicate that leukocyte influx into the lung occurs across alveolar capillaries and postcapillary venules, without mention of alternative sites of migration across larger vessels such as arterioles. 20,29,32,68,69 Intuitively, leukocyte migration across smaller vessels seems most reasonable, given that larger vessels such as arterioles have walls with more complex barriers, including tighter endothelial cell junctions and more compact medial smooth muscle. 70 Nonetheless, the new findings in the present study clearly demonstrate that leukocyte transmigration in both arterioles and venules can occur during acute lung injury.…”

Section: Discussionmentioning

confidence: 99%

Direct Leukocyte Migration across Pulmonary Arterioles and Venules into the Perivascular Interstitium of Murine Lungs during Bleomycin Injury and Repair

Wang

Kachel

Cesta

et al. 2011

The American Journal of Pathology

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During acute lung injury and repair, leukocytes are thought to enter the lung primarily across alveolar capillaries and postcapillary venules. We hypothesized that leukocytes also migrate across pulmonary arterioles and venules, which serve as alternative sites for leukocyte influx into the lung during acute lung injury and repair. Lung sections from C57BL/6J mice up to 14 days after intratracheal bleomycin (3.33 U/kg) or saline instillation were assessed by light, fluorescence, confocal, and transmission electron microscopy for evidence of inflammatory cell sequestration and transmigration at these sites. After bleomycin treatment, large numbers of leukocytes (including neutrophils, eosinophils, and monocytes) were present in the vascular lumina and in perivascular interstitia of pulmonary arterioles and venules, as well as within the vascular walls. Leukocytes were observed within well-defined pathways in arteriolar walls and much less structured pathways in venular walls, apparently in the process of transmigration. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were expressed at sites of leukocyte interaction with the luminal surface, especially in arterioles. Leukocytes appeared to exit from the vessels near collagen fibers into the perivascular interstitium. Results indicate that leukocytes can directly migrate across arteriolar and venular walls into the perivascular interstitium, which may represent an important but under-recognized pathway for leukocyte influx into the lung during injury and repair.

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Section: Discussionmentioning

confidence: 99%

Direct Leukocyte Migration across Pulmonary Arterioles and Venules into the Perivascular Interstitium of Murine Lungs during Bleomycin Injury and Repair

Wang

Kachel

Cesta

et al. 2011

The American Journal of Pathology

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“…Normal (control) ECs were derived from 12 subjects with anemia due to iron or vitamin B 12 deficiency (Vacca et al, 1994). As ECs are phenotypically and functionally site restricted (Aird, 2007) we analyzed these cells from the BM in both patients and controls. The normal ECs were little heterogeneous in terms of expression of FLNA, VIM, CRYAB and YWHAZ because the s.d.…”

Section: Patients and Ecsmentioning

confidence: 99%

Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets

et al. 2011

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Bone marrow (BM) angiogenesis has an important role in the initiation and progression of multiple myeloma (MM). We looked at novel mechanisms of vessel formation in patients with MM through a comparative proteomic analysis between BM endothelial cells (ECs) of patients with active MM (MMECs) and ECs of patients with monoclonal gammopathy of undetermined significance (MGECs) and of subjects with benign anemia (normal ECs). Four proteins were found overexpressed in MMECs: filamin A, vimentin, a-crystallin B and 14-3-3f/d protein, not yet linked to overangiogenic phenotype. These proteins gave a typical distribution in the BM of MM patients and in MMECs versus MGECs, plausibly according to a different functional state. Their expression was enhanced by vascular endothelial growth factor, fibroblast growth factor 2, hepatocyte growth factor and MM plasma cell conditioned medium in step with enhancement of MMEC angiogenesis. Their silencing RNA knockdown affected critical MMEC angiogenesis-related functions, such as spreading, migration and tubular morphogenesis. A gradual stabilization of 14-3-3f/d protein was observed, with transition from normal ECs to MGECs and MMECs that may be a critical step for the angiogenic switch in MMECs and maintenance of the cell overangiogenic phenotype. These proteins were substantially impacted by anti-MM drugs, such as bortezomib, lenalidomide and panobinostat. Results suggest that these four proteins could be new targets for the antiangiogenic management of MM patients.

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“…brain pericytes have a strong phagocytic ability, which may account for their concentrating FG from the vasculature (Kristensson and Olsson, 1973). Another option is that not all endothelial cells may be able to accumulate or transcytose the FG since endothelial cells are well known to exhibit organ-specific phenotypes (Aird, 2007).…”

Section: Discussionmentioning

confidence: 99%

A simple method to fluorescently label pericytes in the CNS and skeletal muscle

Edwards

Singh

Morris

et al. 2013

Microvascular Research

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Pericytes play important roles in vascular control and may form an important part of the blood brain barrier. Here we introduce a simple method for fluorescently labelling pericytes to enable further studies in live or fixed tissue of rats and mice. Following intraperitoneal injection, the fluorescent tracer Fluorogold was rapidly taken up into vascular endothelial cells, and within 3 hours in the central nervous system appeared within small perivascular cells with a morphology consistent with pericytes. These Fluorogold labelled cells were pericytes since they displayed immunoreactivity for platelet derived growth factor receptor beta and were closely associated with isolectin B4 binding to endothelial cells. Pericytes in skeletal muscle were also labelled with this method, but not those within the heart, lungs or kidney. This simple method could therefore be applied for labelling pericytes in a wide variety of studies, including live cell imaging or immunohistochemistry.

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Phenotypic Heterogeneity of the Endothelium

Cited by 972 publications

References 194 publications

Direct Leukocyte Migration across Pulmonary Arterioles and Venules into the Perivascular Interstitium of Murine Lungs during Bleomycin Injury and Repair

Direct Leukocyte Migration across Pulmonary Arterioles and Venules into the Perivascular Interstitium of Murine Lungs during Bleomycin Injury and Repair

Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets

A simple method to fluorescently label pericytes in the CNS and skeletal muscle

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