Circulating fibrocytes and pulmonary arterial hypertension: Figure 1–

Gambaryan, Natalia; Cohen‐Kaminsky, Sylvia; Montani, David; Girerd, Barbara; Huertas, Alice; Seferian, Andrei; Humbert, Marc; Perros, Frédèric

doi:10.1183/09031936.00039811

Cited by 9 publications

(8 citation statements)

References 11 publications

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“…These authors hypothesized that the increased expression of CD11b in fibrocytes reflects their activation in the course of inflammatory response, as in patients with PAH. 34 We report that hypoxic rat lung presents increased CD11b gene expression. Leukocyte recruitment occurs in several steps initiated by selectins.…”

Section: Discussionmentioning

confidence: 99%

“…It is expressed on the surface of many leukocytes, including monocytes; it mediates inflammation by regulating leukocyte adhesion and migration. Perros et al 34 showed an increased expression of CD11b in fibrocytes of PAH patients. CD11b, or α M integrin, is expressed on monocytes in an inactive conformation but can be rapidly activated by factors hitherto unknown.…”

Section: Discussionmentioning

confidence: 99%

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Possible Role of Lysophosphatidic Acid in Rat Model of Hypoxic Pulmonary Vascular Remodeling

Shlyonsky¹,

Naeije²,

Mies³

2014

Pulm. circ.

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Pulmonary hypertension is characterized by cellular and structural changes in the vascular wall of pulmonary arteries. We hypothesized that lysophosphatidic acid (LPA), a bioactive lipid, is implicated in this vascular remodeling in a rat model of hypoxic pulmonary hypertension. Exposure of Wistar rats to 10% O 2 for 3 weeks induced an increase in the mean serum levels of LPA, to 40.9 (log-detransformed standard deviations: 23.4 -71.7) μM versus 21.6 (11.0-42.3) μM in a matched control animal group (P ¼ 0.037). We also observed perivascular LPA immunohistochemical staining in lungs of hypoxic rats colocalized with the secreted lysophospholipase D autotaxin (ATX). Moreover, ATX colocalized with mast cell tryptase, suggesting implication of these cells in perivascular LPA production. Hypoxic rat lungs expressed more ATX transcripts (2.4-fold) and more transcripts of proteins implicated in cell migration: β2 integrin (1.74-fold), intracellular adhesion molecule 1 (ICAM-1; 1.84-fold), and αM integrin (2.70-fold). Serum from the hypoxic group of animals had significantly higher chemoattractant properties toward rat primary lung fibroblasts, and this increase in cell migration could be prevented by the LPA receptor 1 and 3 antagonists. LPA also increased adhesive properties of human pulmonary artery endothelial cells as well as those of human peripheral blood mononuclear cells, via the activation of LPA receptor 1 or 3 followed by the stimulation of gene expression of ICAM-1, β-1, E-selectin, and vascular cell adhesion molecule integrins. In conclusion, chronic hypoxia increases circulating and tissue levels of LPA, which might induce fibroblast migration and recruitment of mononuclear cells in pulmonary vasculature, both of which contribute to pulmonary vascular remodeling.Keywords: anti-lysophosphatidic acid antibody, fibroblast, circulating progenitor cells, cell migration and adhesion. INTRODUCTIONThe chronic-hypoxia model of pulmonary hypertension (PH) is characterized by an important remodeling of the arteriolar wall. This PH model is very predictable and reproducible, and although implication of vasoconstriction and vasoproliferation of the different cell types constituting the vascular wall has been shown, all the factors involved in these mechanisms are not yet identified. [1][2][3][4] Patients with PH can present with thrombotic pulmonary vascular lesions suggesting abnormalities of blood coagulation factors and platelet function. Hypoxia per se may accelerate blood coagulation 5 and platelet adhesion and aggregation. 6 The activation of platelets can result in the release of multiple and diverse soluble mediators such as

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Possible Role of Lysophosphatidic Acid in Rat Model of Hypoxic Pulmonary Vascular Remodeling

Shlyonsky¹,

Naeije²,

Mies³

2014

Pulm. circ.

View full text Add to dashboard Cite

show abstract

“…Although 10 out of 26 patients in the study by YEAGER et al [17] were being treated with prostanoids, no difference was seen in the numbers of fibrocytes in these patients compared with patients on other treatments. In contrast, GAMBARYAN et al [19] report a decrease in percentage of fibrocytes in adult patients with pulmonary arterial hypertension (PAH) but no difference in absolute cell counts. Here, no correlation was found between fibrocyte numbers and any clinical parameter.…”

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confidence: 94%

“…For example, YEAGER et al [17] used CD45 and procollagen with an isotype-controlled flowcytometric technique across the whole white blood cell gate. By contrast, GAMBARYAN et al [19] used CD11b, CD34 and vimentin as markers. Less information is available on the flow-cytometric technique used but it is clear there are significant methodological differences.…”

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confidence: 99%