Increased hyaluronic acid content in idiopathic pulmonary arterial hypertension

¹ Dept of Pharmacology, Aristotle University School of Medicine, Thessaloniki, Greece
² Dept of Medicine, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany

^* To whom correspondence should be addressed. E-mail: oliver.eickelberg{at}innere.med.uni-giessen.de.

	Abstract

Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease characterized by elevated blood pressure in the pulmonary circulation. Initial vasoconstriction, proliferation of pulmonary arterial smooth muscle cells (PASMC), and increased deposition of extracellular matrix (ECM) contribute to pathologic remodelling of pulmonary arterioles in IPAH. Glycosaminoglycans (GAG), components of the ECM, control cellular proliferation and differentiation, but their expression in IPAH remains elusive.

Here, we investigated GAG expression in lungs of patients with IPAH or control transplant donors, and analyzed expression and localization of GAG metabolizing enzymes in vivo and in vitro. We detected a significant increase in the expression of hyaluronic acid (HA) in IPAH lungs, associated with increased hyaluronan synthase (HAS) 1 and decreased hyaluronoglucosaminidase (HYAL) 1 gene expression, assessed by quantitative (q)RT-PCR and Western blotting. HAS1 protein localized to PASMC in vivo, and increased HA deposition was observed in remodelled pulmonary arteries in IPAH. TGF-1, a profibrotic growth factor, led to increased HA secretion and HAS1 expression in primary PASMC.

Our results demonstrate an increased HA content in IPAH lungs, associated with increased HAS1 and decreased HYAL1 gene expression. Synergistic regulation of GAG metabolizing enzymes in favour of accumulation may thus regulate pathologic vascular remodelling in IPAH lungs.

Keywords:  Hyaluronic acid, pulmonary arterial hypertension, pulmonary arterial smooth muscle cells, TGF-1, vascular remodelling

This article has been cited by other articles:

				I. Klagas, S. Goulet, G. Karakiulakis, J. Zhong, M. Baraket, J. L. Black, E. Papakonstantinou, and M. Roth Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD Eur. Respir. J., September 1, 2009; 34(3): 616 - 628. [Abstract] [Full Text] [PDF]

				R. Hamid and J. H. Newman Evidence for Inflammatory Signaling in Idiopathic Pulmonary Artery Hypertension: TRPC6 and Nuclear Factor-{kappa}B Circulation, May 5, 2009; 119(17): 2297 - 2298. [Full Text] [PDF]