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01-03-2013 | Original Contribution

Novel effects of adenosine receptors on pericellular hyaluronan matrix: implications for human smooth muscle cell phenotype and interactions with monocytes during atherosclerosis

Authors: M. Grandoch, J. Hoffmann, K. Röck, F. Wenzel, A. Oberhuber, H. Schelzig, J. W. Fischer

Published in: Basic Research in Cardiology | Issue 2/2013

Abstract

Hyaluronan (HA) is responsive to pro-atherosclerotic growth factors and cytokines and is thought to contribute to neointimal hyperplasia and atherosclerosis. However, the specific function of the pericellular HA matrix is likely depend on the respective stimuli. Adenosine plays an important role in the phenotypic regulation of vascular smooth muscle cells (VSMC) and is thought to inhibit inflammatory responses during atherosclerosis. The aim of this study was to examine the regulation and function of HA matrix in response to adenosine in human coronary artery SMC (HCASMC). The adenosine receptor agonist NECA (10 μM) caused a strong induction of HA synthase (HAS)1 at 6 h and a weaker induction again after 24 h. Use of selective adenosine receptor antagonists revealed that adenosine A2_B receptors (A2_BR) mediate the early HAS1 induction, whereas late HAS1 induction was mediated via A2_AR and A3R. The strong response after 6 h was mediated in part via phosphoinositide-3 kinase- and mitogen-activated protein kinase pathways and was inhibited by Epac. Functionally, NECA increased cell migration, which was abolished by shRNA-mediated knock down of HAS1. In addition to HA secretion, NECA also stimulated the formation of pronounced pericellular HA matrix in HCASMC and increased the adhesion of monocytes. The adenosine-induced monocyte adhesion was sensitive to hyaluronidase. In conclusion, the current data suggest that adenosine via adenosine A2_BR and A2_AR/A3R induces HAS1. In turn a HA-rich matrix is formed by HCASMC which likely supports the migratory HCASMC phenotype and traps monocytes/macrophages in the interstitial matrix.

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Title: Novel effects of adenosine receptors on pericellular hyaluronan matrix: implications for human smooth muscle cell phenotype and interactions with monocytes during atherosclerosis
Authors: M. Grandoch
J. Hoffmann
K. Röck
F. Wenzel
A. Oberhuber
H. Schelzig
J. W. Fischer
Publication date: 01-03-2013
Publisher: Springer-Verlag
Published in: Basic Research in Cardiology / Issue 2/2013
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-013-0340-6

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