Science and Research

Functional and molecular factors associated with TAPSE in hypoxic pulmonary hypertension

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 alpha- and beta-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.

  • Crnkovic, S.; Schmidt, A.; Egemnazarov, B.; Wilhelm, J.; Marsh, L. M.; Ghanim, B.; Klepetko, W.; Olschewski, A.; Olschewski, H.; Kwapiszewska, G.

Keywords

  • Animals
  • Cell Hypoxia
  • Heart Ventricles/metabolism/*pathology/physiopathology
  • Hypertension, Pulmonary/diagnostic imaging/metabolism/*physiopathology
  • Hypertrophy, Right Ventricular/diagnostic imaging/metabolism/pathology
  • Male
  • Mice
  • Muscle Proteins/genetics/metabolism
  • Myocardium/metabolism
  • Receptors, Interleukin/blood
  • Transcriptome
  • Tricuspid Valve/*pathology
  • Ventricular Function, Right
  • Ventricular Remodeling
  • Il22ra2
  • Tapse
  • hypoxia
  • pulmonary hypertension
Publication details
DOI: 10.1152/ajplung.00381.2015
Journal: American journal of physiology. Lung cellular and molecular physiology
Pages: L59-73 
Number: 1
Work Type: Original
Location: UGMLC
Disease Area: PH
Partner / Member: JLU
Access-Number: 27106290
See publication on PubMed

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