P157 Hepatocyte growth factor concentration correlates with haemodynamic severity in connective tissue disease-associated pulmonary arterial hypertension. (14th November 2013)

• Record Type: Journal Article
• Authors: Condliffe, R; Elliot, CA; Sabroe, I; Zamanian, RT; Morton, A; Swift, AJ; Kiely, DG; Lawrie, A
• Is Part Of: Thorax. Volume 68(2013)Supplement 3
• Page Start: A146
• Page End: A147
• Publication Date: 2013-11-14
• Subjects: Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thoraxjnl-2013-204457.308
• Languages: English
• ISSNs: 0040-6376

Abstract

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: Ono M et al . Circulation 2004;110:2896–92 Hiramine K et al . Int J Molec Med 2011;27:497–502