Multiple roles of macrophage migration inhibitory factor in pulmonary hypertension

Jalce, Gaël; Guignabert, Christophe

doi:10.1152/ajplung.00234.2019

Cited by 16 publications

(9 citation statements)

References 66 publications

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“…As a pleiotropic upstream proinflammatory mediator, MIF is a promising molecular target for PH therapy because MIF contributes to perivascular inflammation and pulmonary artery remodeling (Jalce & Guignabert, 2020). In addition, the increase in MIF levels in the pulmonary artery of PH will induce the proliferation of pulmonary vascular smooth muscle cells, leading to pulmonary artery remodeling (Li et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Impact of Parthanatos on the Increased Risk of Onset and Mortality in Male Patients With Pulmonary Hypertension

Wang

et al. 2021

Am J Mens Health

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There have been no studies as to whether parthanatos, a poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1)-dependent and apoptosis-inducing factor (AIF)-mediated caspase-independent programmed cell death, is present in pulmonary hypertension (PH). Basic studies have, however, been conducted on several of the key molecules in parthanatos, such as PARP-1, AIF, and macrophage migration inhibitory factor (MIF). For this study, we collected blood samples from 88 incident male patients with PH and 50 healthy controls at the Shanghai Pulmonary Hospital. We measured the key factors of parthanatos (PARP-1, PAR, AIF, and MIF) by enzyme-linked immunosorbent assay and performed a logistic regression, Cox proportional hazards analysis, and Kaplan–Meier test to assess the prognostic value of the key molecules in diagnosing and predicting survival. The patients who ultimately died had a significantly poorer clinical status during the study than those who survived. The PARP-1, PAR, AIF, and MIF levels were significantly higher in the patients than in the controls (all p < .0001), and the PARP-1, PAR, and AIF levels were higher in the nonsurvivors than in the survivors (all p < .0001). PARP-1 and AIF levels served as independent predictors of disease onset and mortality in these patients (all p < .005). Patients with PARP-1 levels <11.24 ng/mL or AIF levels <1.459 pg/mL had significantly better survival than those with higher PARP-1 or AIF levels ( p < .0001). Circulating levels of PARP-1 and AIF were independent predictors for PH onset and mortality, which indicated that parthanatos might be associated with the pathogenesis of PH.

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Section: Discussionmentioning

confidence: 99%

Impact of Parthanatos on the Increased Risk of Onset and Mortality in Male Patients With Pulmonary Hypertension

Wang

et al. 2021

Am J Mens Health

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“…The concept that perivascular inflammation may be a driver and marker of vascular remodeling has also been explored recently as another approach for molecular imaging of disease activity in PAH, based on a body of literature that has identified a variety of perivascular inflammatory lineages in human PAH and experimental PH lung tissues. [167][168][169][170] A 68 Ga-substituted conjugate molecule containing mannosylated human serum albumin protein ( 68 Ga-NOTA-MSA) has been used as a PET-CT imaging probe targeting macrophages expressing the mannose receptor (CD206). 171 In support of enhanced macrophage activity associated with PH biology, the investigators found transcriptional signatures consistent with increased macrophage activation, and immunohistologic evidence of CD206 + macrophage infiltration in the perivascular tissues of rats with monocrotaline-induced PH, all of which were progressive with development of the PH phenotype.…”

Section: Ga-nota-msa Pet-ctmentioning

confidence: 99%

Novel Approaches to Imaging the Pulmonary Vasculature and Right Heart

Alenezi

Covington

Mukherjee³

et al. 2022

Circulation Research

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There is an increased appreciation for the importance of the right heart and pulmonary circulation in several disease states across the spectrum of pulmonary hypertension and left heart failure. However, assessment of the structure and function of the right heart and pulmonary circulation can be challenging, due to the complex geometry of the right ventricle, comorbid pulmonary airways and parenchymal disease, and the overlap of hemodynamic abnormalities with left heart failure. Several new and evolving imaging modalities interrogate the right heart and pulmonary circulation with greater diagnostic precision. Echocardiographic approaches such as speckle-tracking and 3-dimensional imaging provide detailed assessments of regional systolic and diastolic function and volumetric assessments. Magnetic resonance approaches can provide high-resolution views of cardiac structure/function, tissue characterization, and perfusion through the pulmonary vasculature. Molecular imaging with positron emission tomography allows an assessment of specific pathobiologically relevant targets in the right heart and pulmonary circulation. Machine learning analysis of high-resolution computed tomographic lung scans permits quantitative morphometry of the lung circulation without intravenous contrast. Inhaled magnetic resonance imaging probes, such as hyperpolarized 129Xe magnetic resonance imaging, report on pulmonary gas exchange and pulmonary capillary hemodynamics. These approaches provide important information on right ventricular structure and function along with perfusion through the pulmonary circulation. At this time, the majority of these developing technologies have yet to be clinically validated, with few studies demonstrating the utility of these imaging biomarkers for diagnosis or monitoring disease. These technologies hold promise for earlier diagnosis and noninvasive monitoring of right heart failure and pulmonary hypertension that will aid in preclinical studies, enhance patient selection and provide surrogate end points in clinical trials, and ultimately improve bedside care.

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“…We further examined specific ligand-receptor interactions and found that signaling molecules known to play a role in PAH such as vascular endothelial growth factor A (VEGFA) (32), C-X-C motif chemokine ligand 12 (CXCL12) (33,34), and macrophage migration inhibitory factor (MIF) (35,36) were not only differentially active in PAH models compared to control but also specific to cell-cell communication involving EA2 but not EA1 (Figure 2C) nor EC (Figure E3).…”

Section: Ea2-specific Cell-to-cell Signaling Network Are Activated In Pahmentioning

confidence: 99%

ATm4sf1-Marked Subpopulation of Endothelial Stem/Progenitor Cells Identified by Lung Single-Cell Omics of Pulmonary Arterial Hypertension

Hong

Wong

Huynh

et al. 2022

Preprint

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Rationale: The identification and role of endothelial progenitor cells (EPCs) in pulmonary arterial hypertension (PAH) remains controversial. Single-cell omics analysis can shed light on EPCs and their potential contribution to PAH pathobiology. Objectives: We aim to identify EPCs in rat lungs and assess their relevance to preclinical and human PAH. Methods: Differential expression, gene set enrichment, cell-cell communication, and trajectory reconstruction analyses were performed on lung endothelial cells from single-cell RNA-seq of Sugen-hypoxia, monocrotaline, and control rats. Relevance to human PAH was assessed in multiple independent blood and lung transcriptomic datasets. Measurements and Main Results: A subpopulation of endothelial cells (EA2) marked by Tm4sf1, a gene strongly implicated in cancer, harbored a distinct transcriptomic signature including Bmpr2 downregulation that was enriched for pathways such as inflammation and angiogenesis. Cell-to-cell communication networks specific to EA2 were activated in PAH such as CXCL12 signaling. Trajectory analysis demonstrated EA2 has a stem/progenitor cell phenotype. Analysis of independent datasets revealed Tm4sf1 is a marker for hematopoietic stem cells and is upregulated in PAH peripheral blood, particularly in patients with worse WHO functional class. EA2 signature genes including Procr and Sulf1 were found to be differentially regulated in the lungs of PAH patients and in PAH models in vitro, such as BMPR2 knockdown. Conclusions: Our study uncovered a novel Tm4sf1-marked stem/progenitor subpopulation of rat lung endothelial cells and demonstrated its relevance to preclinical and human PAH. Future experimental studies are warranted to further elucidate the pathogenic role and therapeutic potential of targeting EA2 and Tm4sf1 in PAH.

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Multiple roles of macrophage migration inhibitory factor in pulmonary hypertension

Cited by 16 publications

References 66 publications

Impact of Parthanatos on the Increased Risk of Onset and Mortality in Male Patients With Pulmonary Hypertension

Impact of Parthanatos on the Increased Risk of Onset and Mortality in Male Patients With Pulmonary Hypertension

Novel Approaches to Imaging the Pulmonary Vasculature and Right Heart

ATm4sf1-Marked Subpopulation of Endothelial Stem/Progenitor Cells Identified by Lung Single-Cell Omics of Pulmonary Arterial Hypertension

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