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  Mitochondrial Respiration in Peripheral Blood Mononuclear Cells Negatively Correlates with Disease Severity in Pulmonary Arterial Hypertension

Sommer, N., Theine, F. F., Pak, O., Tello, K., Richter, M., Gall, H., et al. (2022). Mitochondrial Respiration in Peripheral Blood Mononuclear Cells Negatively Correlates with Disease Severity in Pulmonary Arterial Hypertension. JOURNAL OF CLINICAL MEDICINE, 11(14): 4132. doi:10.3390/jcm11144132.

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Sommer, Natascha, Autor
Theine, Finn Fabian, Autor
Pak, Oleg, Autor
Tello, Khodr, Autor
Richter, Manuel, Autor
Gall, Henning, Autor
Wilhelm, Jochen1, Autor           
Savai, Rajkumar1, Autor           
Weissmann, Norbert, Autor
Seeger, Werner1, Autor           
Ghofrani, Hossein A., Autor
Hecker, Matthias, Autor
Affiliations:
1Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591698              

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 Zusammenfassung: Mitochondrial and immune cell dysfunction contributes to the development of pulmonary arterial hypertension (PAH). We thus aimed to investigate mitochondrial respiration and mitochondrial gene expression patterns in the peripheral blood mononuclear cells (PBMC) of patients with idiopathic and hereditary PAH and their correlation to disease parameters. Mitochondrial respiration determined using high-resolution respirometry was not significantly different in PBMC when comparing an outpatient cohort of PAH patients with healthy controls. However, when directly comparing mitochondrial respiration to the hemodynamic parameters of an inpatient PAH cohort, mitochondrial respiration negatively correlated with pulmonary vascular resistance (PVR) and positively correlated with the cardiac index (CI). Furthermore, microarray analysis shows upregulation of mitochondrial erythroid-specific 5-aminolevulinate synthase 2 (ALAS2), as well as the regulation of genes involved in iron and heme metabolism, in the PBMC of patients with PAH, with ALAS2 upregulation in PAH patients being confirmed on the protein level. Multiple regression analysis with age and gender as confounders showed that both PVR and hemoglobin content negatively correlated with maximal respiration. Therefore, we conclude that mitochondrial function in the PBMC of PAH patients is affected by disease severity. However, further studies to investigate cell-type-specific alterations and functional consequences are necessary.

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 Datum: 2022-07-16
 Publikationsstatus: Online veröffentlicht
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 Identifikatoren: ISI: 000832196500001
DOI: 10.3390/jcm11144132
PMID: 35887896
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Titel: JOURNAL OF CLINICAL MEDICINE
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 11 (14) Artikelnummer: 4132 Start- / Endseite: - Identifikator: -