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001-es BibID:	BIBFORM059179
Első szerző:	Moser, Bernhard
Cím:	Local and Systemic RAGE Axis Changes in Pulmonary Hypertension: CTEPH and iPAH / Bernhard Moser, Anna Megerle, Christine Bekos, Stefan Janik, Tamás Szerafin, Peter Birner, Ana-Iris Schiefer, Michael Mildner, Irene Lang, Nika Skoro-Sajer, Roela Sadushi-Kolici, Shahrokh Taghavi, Walter Klepetko, Hendrik Jan Ankersmit
Dátum:	2014
ISSN:	1932-6203
Megjegyzések:	Objective: The molecular determinants of chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH) remain poorly understood. The receptor for advanced glycation endproducts (RAGE) and its ligands: HMGB1 and S100A9 are involved in inflammatory disorders. We sought to investigate the role of the RAGE axis in patients with CTEPH undergoing pulmonary endarterectomy (PEA), iPAH undergoing lung transplantation (LuTX). The high pulmonary vascular resistance in CTEPH/iPAH results in pressure overload of the right ventricle. We compared sRAGE measurements to that of patients with aortic valve stenosis (AVS) - pressure overload of the left ventricle. Methods: We enrolled patients with CTEPH(26), iPAH(15), AVS(15) and volunteers(33). Immunohistochemistry with antibodies to RAGE and HMGB1 was performed on PEA specimens and lung tissues. We employed enzyme-linked immunosorbent assays to determine the concentrations of sRAGE, esRAGE, HMGB1 and S100A9 in serum of volunteers and patients with CTEPH, iPAH, AVS before and after PEA, LuTX and aortic valve replacement (AVR). Results: In endarterectomised tissues from patients with CTEPH RAGE and HMGB1 were identified in myofibroblasts (aSMA+ vimentin+ CD342), recanalizing vessel-like structures of distal myofibrotic tissues and endothelium of neointima. RAGE was differentially expressed in prototypical Heath Edwards lesions in iPAH. We found significantly increased serum concentrations of sRAGE, esRAGE and HMGB1 in CTEPH. In iPAH, sRAGE and esRAGE were significantly higher than in controls. Serum concentrations of sRAGE were significantly elevated in iPAH(p,0.001) and CTEPH(p = 0.001) compared to AVS. Serum sRAGE was significantly higher in iPAH compared to CTEPH(p = 0.042) and significantly reduced in AVS compared to controls(p = 0.001). There were no significant differences in sRAGE serum concentrations before and after surgical therapy for CTEPH, iPAH or AVS. Conclusions: Our data suggest a role for the RAGE pathway in the pathophysiology of CTEPH and iPAH. PEA improves the local control of disease but may not influence the systemic inflammatory mechanisms in CTEPH patients through the RAGE pathway.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Blood pressure Chronic obstructive pulmonary disease Fibroblasts Glycation Lung transplantation Pulmonary arteries Pulmonary hypertension Surgical and invasive medical procedures
Megjelenés:	Plos One. - 9 : 9 (2014), p. e106440-. -
További szerzők:	Megerle, Anna Bekos, Christine Janik, Stefan Szerafin Tamás (1960-) (szívsebész, mellkassebész) Birner, Peter Schiefer, Ana-Iris Mildner, Michael Lang, Irene Skoro-Sajer, Nika Sadushi-Kolici, Roela Taghavi, Shahrokh Klepetko, Walter Ankersmit, Hendrik Jan
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