Pneumologie 2012; 66 - A704
DOI: 10.1055/s-0032-1315536

A potential role of high mobility group box-1 (HGMB1) in inflammatory vascular remodelling

H Xu 1, 2, D Zabini 2, A Olschewski 1, 2, G Kwapiszewska 1, LM Marsh 1
  • 1Ludwig Boltzmann Institute for Lung Vascular Research, Graz
  • 2Experimental Anesthesiology, Department of Anesthesia and Intensive Care Medicine, Medical University of Graz

Pulmonary hypertension (PH) is a life threatening disease characterised by a progressive remodelling of the pulmonary arteries. Recently, inflammatory processes have been implicated in the development and progression of PH.

High mobility group box-1 (HGMB1) is a nuclear protein that acts to stabilise nucleosome formation and regulates transcription. Extracellularly, HGMB1 has an important role in mediating the inflammatory response, acting not only as an endogenous danger signal but also as a chemoattractant. Additionally, HMGB1 has been implicated in several pathological conditions including rheumatic disease, sepsis and myocardial infarction.

We here have investigated the role of HMGB1 in an inflammatory model exhibiting pronounced vascular remodelling. Exposure of mice to house dust mite (HDM) resulted in a robust inflammatory response characterised by accumulation of inflammatory cells in the bronchoalveolar lavage and most importantly around remodelled vessels. Immunohistochemistry revealed HGMB1 expression in HDM treated mice was predominately localised to areas of peribronchial and perivascular inflammation.

Our preliminary data indicates that increased HGMB1 levels may adversely affect pulmonary haemostasis, leading to vascular remodelling. However, further studies are required to validate this hypothesis.