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P157 Hepatocyte growth factor concentration correlates with haemodynamic severity in connective tissue disease-associated pulmonary arterial hypertension
  1. R Condliffe1,
  2. CA Elliot1,
  3. I Sabroe2,
  4. RT Zamanian3,
  5. A Morton4,
  6. AJ Swift5,
  7. DG Kiely1,
  8. A Lawrie6
  1. 1Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
  2. 2Department of Infection and Immunity, University of Sheffield, Sheffiled, UK
  3. 3Stanford University, Palo Alto, USA
  4. 4Department of Cardiology, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK
  5. 5Academic Unit of Radiology, University of Sheffield, Sheffield, UK
  6. 6Department of Cardiovascular Science, University of Sheffield, Sheffield, UK

Abstract

Introduction Hepatocyte growth factor (HGF) acts via the tyrosine kinase receptor, c-MET, on endothelial and epithelial cells. It has angiogenic, mitogenic, motogenic and anti-apoptotic effects. Administration of HGF has been shown to ameliorate pulmonary arterial hypertension (PAH) in the monocrotaline rat model.1,2 Little is known regarding circulating HGF levels in human disease.

Methods 47 incident, treatment naive patients with PAH in association with connective tissue disease (CTD-PAH) had blood sampling at or within 1 day of diagnostic right heart catheterisation. Plasma HGF concentrations were measured using Bio-Plex bead array. A proportion of patients also had NT-proBNP measured and underwent cardiac MRI.

Results Baseline characteristics were (mean, sd): Age 64(10)yrs, mean right atrial pressure (mRAP) 9.6(11.7)mmHg, mean pulmonary arterial pressure (mPAP) 40.6(13)mmHg, pulmonary arterial wedge pressure 10.5(4.5)mmHg, cardiac index (CI) 2.97(0.7)L/min, pulmonary vascular resistance (PVR) 531(350)dyns. HGF levels correlated positively with mRAP (0.6, r < 0.001), mPAP (r = 0.68, p < 0.001: fig 1), PVR (r = 0.51, p = 0.001) and negatively with CI (r = -0.43, p = 0.008) and right ventricular ejection fraction measured by MRI (r = -0.53, p = 0.034). N-terminal pro B-type natriuretic peptide (NT-proBNP) measured in approximately 50% of patients correlated more strongly with CI (r = -0.72, p < 0.001) and PVR (r = 0.61, p = 0.003) but did not correlate with mPAP. A small proportion (7) of patients underwent repeat right heart catheterisation (RHC) following therapy with Bosentan (n = 6) or sildenafil (n = 1). Interestingly, improvement in CI at repeat RHC correlated positively with a further increase in HGF levels (r = 0.8, p = 0.03).

Conclusion Plasma HGF concentrations correlate with haemodynamic severity in CTD-PAH. Further work to determine whether high levels of HGF are involved in the pathogenesis of PAH or are instead elevated in a reparative response to underlying pulmonary vascular remodelling is required.

References

  1. Ono M et al. Circulation 2004;110:2896–92

  2. Hiramine K et al. Int J Molec Med 2011;27:497–502

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