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Disconnect between Fibrotic Response and Right Ventricular Dysfunction.

Slaven Crnkovic1, Bakytbek Egemnazarov1, Rachel Damico2

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|December 18, 2018
PubMed
Summary
This summary is machine-generated.

Galectin-3 drives right ventricle fibrosis in pulmonary hypertension by expanding cardiac fibroblasts. However, targeting this fibrosis did not improve right ventricle function in this study.

Keywords:
PDGFRαgalectin-3right ventricle fibrosisright ventricular function

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Area of Science:

  • Cardiovascular Research
  • Pulmonary Hypertension Pathophysiology
  • Fibrosis Mechanisms

Background:

  • Right ventricle (RV) remodeling and fibrosis are linked to dysfunction and poor survival in pulmonary hypertension (PH).
  • Understanding the cellular changes and fibrosis modulation in the RV is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of galectin-3 in RV fibrosis development and its impact on RV function.
  • To explore the cellular mechanisms underlying RV fibrosis in PH models.

Main Methods:

  • Assessed fibrotic markers in RVs from PH patients and animal models (murine pulmonary artery banding, rat monocrotaline/Sugen5416-hypoxia).
  • Utilized galectin-3 knockout/inhibitor-treated mice and pirfenidone for antifibrotic treatment.
  • Performed invasive hemodynamics and echocardiography to evaluate RV function.

Main Results:

  • Marked galectin-3 expression and proliferating RV fibroblasts characterized established fibrosis.
  • Galectin-3 inhibition and pirfenidone reduced RV fibrosis progression in a PH model but did not improve RV function.
  • RV fibrotic regions contained vimentin/PDGFRα-expressing mesenchymal cells, lacking αSMA.
  • Elevated serum galectin-3 in idiopathic pulmonary arterial hypertension patients did not correlate with cardiac function.

Conclusions:

  • Extrapulmonary galectin-3 mediates RV fibrosis in PH by expanding PDGFRα/vimentin-expressing cardiac fibroblasts.
  • Despite effectively targeting fibrosis, interventions showed no significant beneficial effects on RV function in this study.