Hematological disorders and pulmonary hypertension

Mathew, Rajamma; Huang, Jing; Wu, Joseph M.; Fallon, John T.; Gewitz, Michael H.

doi:10.4330/wjc.v8.i12.703

Cited by 43 publications

(30 citation statements)

References 175 publications

(165 reference statements)

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“…Furthermore, pulmonary vascular endothelial dysfunction is an important initiating factor in the development of PH 37. Our data showed that IL-17 significantly enhanced the angiogenesis of PAECs, which is consistent with the observation of Numasaki et al 38.…”

Section: Discussionsupporting

confidence: 93%

Targeting IL-17 attenuates hypoxia-induced pulmonary hypertension through downregulation of β-catenin

Wang

Liu

Wang

et al. 2019

Thorax

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BackgroundThe role of interleukin 17 (IL-17) in hypoxic pulmonary hypertension (HPH) remains unclear. This study is designed to explore whether IL-17 is a potential target for HPH treatment.MethodsClinic samples from the lung tissue and serum were obtained from qualified patients. Western blotting, immunohistochemistry and/or ELISA were used to measure the expression of relevant proteins. HPH models were established in C57BL/6 wild-type (WT) and IL-17 −/− mice and were treated with exogenous recombinant mouse IL-17 (rmIL-17) or an IL-17 neutralising antibody. Assays for cell proliferation, angiogenesis and adhesion were employed to analyse the behaviours of human pulmonary arterial endothelial cells (HPAECs). A non-contact Transwell coculture model was used to evaluate intercellular interactions.ResultsExpression of IL-17 was increased in lung tissue of both patients with bronchiectasis/COPD-associated PH and HPH mouse model. Compared with WT mice, IL-17 −/− mice had attenuated HPH, whereas administration of rmIL-17 aggravated HPH. In vitro, recombinant human IL-17 (rhIL-17) promoted proliferation, angiogenesis and adhesion in HPAECs through upregulation of Wnt3a/β-catenin/CyclinD1 pathway, and siRNA-mediated knockdown of β-catenin almost completely reversed this IL-17-mediated phenomena. IL-17 promoted the proliferation but not the migration of human pulmonary arterial smooth muscle cells (HPASMCs) cocultured with HPAECs under both normoxia and hypoxia, but IL-17 had no direct effect on proliferation and migration of HPASMCs. Blockade of IL-17 with a neutralising antibody attenuated HPH in WT mice.ConclusionsIL-17 contributes to the pathogenesis of HPH through upregulation of β-catenin expression. Targeting IL-17 might provide potential benefits for alternative therapeutic strategies for HPH.

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Section: Discussionsupporting

confidence: 93%

Targeting IL-17 attenuates hypoxia-induced pulmonary hypertension through downregulation of β-catenin

Wang

Liu

Wang

et al. 2019

Thorax

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“…This case is consistent with what is known regarding chronic myeloproliferative disorders associated with pulmonary hypertension, whereby there are multiple attributable causes described [41], similar to the noted heterogeneous etiologies of pulmonary hypertension after treatment with bone marrow transplant [42,43]. …”

Section: Pulmonary Hypertension and Myeloid Cell Disorderssupporting

confidence: 89%

Myeloid-Derived Suppressor Cells and Pulmonary Hypertension

Bryant

Mehrad

Brusko

et al. 2018

IJMS

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Myeloid–derived suppressor cells (MDSCs) comprised a heterogeneous subset of bone marrow–derived myeloid cells, best studied in cancer research, that are increasingly implicated in the pathogenesis of pulmonary vascular remodeling and the development of pulmonary hypertension. Stem cell transplantation represents one extreme interventional strategy for ablating the myeloid compartment but poses a number of translational challenges. There remains an outstanding need for additional therapeutic targets to impact MDSC function, including the potential to alter interactions with innate and adaptive immune subsets, or alternatively, alter trafficking receptors, metabolic pathways, and transcription factor signaling with readily available and safe drugs. In this review, we summarize the current literature on the role of myeloid cells in the development of pulmonary hypertension, first in pulmonary circulation changes associated with myelodysplastic syndromes, and then by examining intrinsic myeloid cell changes that contribute to disease progression in pulmonary hypertension. We then outline several tractable targets and pathways relevant to pulmonary hypertension via MDSC regulation. Identifying these MDSC-regulated effectors is part of an ongoing effort to impact the field of pulmonary hypertension research through identification of myeloid compartment-specific therapeutic applications in the treatment of pulmonary vasculopathies.

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“…Pulmoner hipertansiyonun patofizyolojisi ile ilgili çeşitli teoriler mevcuttur. Endotelyal disfonksiyona bağlı doku hipoksisi, anemiye bağlı yüksek kardiyak output ve demir birikimine bağlı oksidatif doku hasarı nedeniyle pulmoner vasküler remodelling gibi çeşitli mekanizmalar öne sürülmüştür [5] . Gerek talasemi intermediada gerekse talasemi majörde eski çalışmalar pulmoner hipertansiyon sıklığının %65-70 arasın-da olduğu bildirse de [6,7] daha yeni çalışmalarda bu oranın %10'larda olduğu görülmektedir [8] .…”

Section: Discussionunclassified