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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Nikam, VS; Schermuly, RT; Dumitrascu, R; Weissmann, N; Kwapiszewska, G; Morrell, N; Klepetko, W; Fink, L; Seeger, W; Voswinckel, R.
Treprostinil inhibits the recruitment of bone marrow-derived circulating fibrocytes in chronic hypoxic pulmonary hypertension.
Eur Respir J. 2010; 36(6):1302-1314 Doi: 10.1183/09031936.00028009 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Kwapiszewska-Marsh Grazyna
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Abstract:
A unique subpopulation of peripheral blood mononuclear cells that exhibit a parallel expression of haematopoietic and mesenchymal markers has been described as "circulating fibrocytes". These cells were demonstrated to obtain a fibroblastic phenotype in tissues or cell culture and contribute to pulmonary fibrotic disorders and tissue remodelling processes. The aim of our study was to characterise the recruitment of circulating fibrocytes in vivo in the model of chronic hypoxic pulmonary hypertension in mice and to analyse the therapeutic effect of the stable prostacyclin analogue trepostinil with respect to this cell population. To track circulating fibrocytes in vivo, we transplanted wild-type mice with bone marrow from ubiquitously eGFP expressing mice and subjected them to chronic hypoxia. We observed significantly increased recruitment of circulating fibrocytes to the remodelled pulmonary resistance arteries in response to hypoxia. Treatment with treprostinil significantly reduced the recruitment of these cells compared to normoxic mice. Treprostinil also reduced right ventricular systolic pressure and slightly reduced the vascular remodelling but failed to reverse the right ventricular hypertrophy. In summary, we show that circulating fibrocytes contribute to hypoxic pulmonary vascular remodelling and may be specifically targeted by a prostacyclin analogue. Further investigations of cellular and paracrine mechanisms are warranted to decipher their role in pulmonary hypertension.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Anoxia - physiopathology
Antihypertensive Agents - pharmacokinetics
Blood Circulation -
Blood Vessels - drug effects
Bone Marrow Cells - drug effects
Chimerism -
Chronic Disease -
Epoprostenol - analogs & derivatives
Female -
Fibroblasts - drug effects
Humans -
Hypertension, Pulmonary - blood
Hypertrophy, Right Ventricular - drug therapy
Leukocytes, Mononuclear - drug effects
Lung - blood supply
Male -
Mice -
Mice, Inbred C57BL -
Mice, Transgenic -
Muscle, Smooth, Vascular - drug effects
Pulmonary Artery - drug effects

Find related publications in this database (Keywords)
Circulating fibrocytes
prostacyclin
pulmonary hypertension
pulmonary vascular disease
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