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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, ³ Both authors contributed equally to this article.

CORRESPONDENCE: O. Eickelberg, University of Giessen Lung Center, Dept of Medicine II, Aulweg 123, Room 6-11, D-35392 Giessen, Germany. Fax: 49 6419942309. E-mail: oliver.eickelberg{at}innere.med.uni-giessen.de

Keywords: Hyaluronic acid, pulmonary arterial hypertension, pulmonary arterial smooth muscle cells, transforming growth factor-β1, vascular remodelling

Received: November 26, 2007
Accepted August 15, 2008

Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease characterised 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 pathological remodelling of pulmonary arterioles in IPAH. Glycosaminoglycans (GAGs), components of the ECM, control cellular proliferation and differentiation, but their expression in IPAH remains elusive.

In the present study, GAG expression was investigated in the lungs of patients with IPAH or control transplant donors, and expression and localisation of GAG-metabolising enzymes were analysed in vivo and in vitro.

A significant increase in the expression of hyaluronic acid (HA) was detected in IPAH lungs, associated with increased hyaluronan synthase (Has)1 and decreased hyaluronoglucosaminidase 1 gene expression, as assessed by quantitative RT-PCR and Western blotting. HAS1 protein localised to PASMC in vivo and increased HA deposition was observed in remodelled pulmonary arteries in IPAH. Transforming growth factor-β1, a profibrotic growth factor, led to increased HA secretion and HAS1 expression in primary PASMC.

The results demonstrate an increased hyaluronic acid content in idiopathic pulmonary arterial hypertension lungs, associated with increased hyaluronan synthase 1 and decreased hyaluronoglucosaminidase 1 gene expression. Synergistic regulation of glycosaminoglycan-metabolising enzymes in favour of accumulation may, thus, regulate pathological vascular remodelling in idiopathic pulmonary arterial hypertension lungs.

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