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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Crnkovic, S; Schmidt, A; Egemnazarov, B; Wilhelm, J; Marsh, LM; Ghanim, B; Klepetko, W; Olschewski, A; Olschewski, H; Kwapiszewska, G.
Functional and molecular factors associated with TAPSE in hypoxic pulmonary hypertension.
Am J Physiol Lung Cell Mol Physiol. 2016; 311(1):L59-L73 Doi: 10.1152/ajplung.00381.2015 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Crnkovic Slaven
Olschewski Horst
Schmidt Albrecht
Co-Autor*innen der Med Uni Graz
Egemnazarov Bakytbek
Kwapiszewska-Marsh Grazyna
Marsh Leigh
Olschewski Andrea

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Adaptation of the right ventricle (RV) to increased afterload is crucial for survival in pulmonary hypertension (PH), but it is challenging to assess RV function and identify associated molecular mechanisms. The aim of the current study was to analyze the relationship between invasive and noninvasive parameters of RV morphology and function and associated molecular changes. The response of mice to normobaric hypoxia was assessed by hechocardiography, invasive hemodynamics, and histological and molecular analyses. Plasma levels of possibly novel markers of RV remodeling were measured by ELISA in patients with idiopathic pulmonary arterial hypertension (IPAH) and matched healthy controls. Chronic hypoxia-induced PH was accompanied by significantly decreased tricuspid annular plane systolic excursion (TAPSE) and unchanged RV contractility index and tau. RV hypertrophy was present without an increase in fibrosis. There was no change in α- and β-major histocompatibility class or natriuretic peptides expression. Comparative microarray analysis identified two soluble factors, fibroblast growth factor-5 (FGF5) and interleukin-22 receptor alpha-2 (IL22RA2), as being possibly associated with RV remodeling. We observed significantly higher plasma levels of IL22RA2, but not FGF5, in patients with IPAH. Hypoxic pulmonary hypertension in a stage of RV remodeling with preserved systolic function is associated with decreased pulmonary vascular compliance, mild diastolic RV dysfunction, and significant decrease in TAPSE. Subtle gene expression changes in the RV vs. the left ventricle upon chronic hypoxia suggest that the majority of changes are due to hypoxia and not due to changes in afterload. Increased IL22RA2 levels might represent a novel RV adaptive mechanism. Copyright © 2016 the American Physiological Society.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Cell Hypoxia -
Heart Ventricles - metabolism
Heart Ventricles - pathology
Heart Ventricles - physiopathology
Hypertension, Pulmonary - diagnostic imaging
Hypertension, Pulmonary - metabolism
Hypertension, Pulmonary - physiopathology
Hypertrophy, Right Ventricular - diagnostic imaging
Hypertrophy, Right Ventricular - metabolism
Hypertrophy, Right Ventricular - pathology
Male -
Mice -
Muscle Proteins - genetics
Muscle Proteins - metabolism
Myocardium - metabolism
Receptors, Interleukin - blood
Transcriptome -
Tricuspid Valve - pathology
Ventricular Function, Right -
Ventricular Remodeling -

Find related publications in this database (Keywords)
pulmonary hypertension
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