Journalartikel
Autorenliste: Dahal, Bhola Kumar; Cornitescu, Teodora; Tretyn, Aleksandra; Pullamsetti, Soni Savai; Kosanovic, Djuro; Dumitrascu, Rio; Ghofrani, Hossein Ardeschir; Weissmann, Norbert; Voswinckel, Robert; Banat, Gamal-Andre; Seeger, Werner; Grimminger, Friedrich; Schermuly, Ralph Theo
Jahr der Veröffentlichung: 2010
Seiten: 158-167
Zeitschrift: American Journal of Respiratory and Critical Care Medicine
Bandnummer: 181
Heftnummer: 2
ISSN: 1073-449X
eISSN: 1535-4970
DOI Link: https://doi.org/10.1164/rccm.200811-1682OC
Verlag: American Thoracic Society
Rationale: Epidermal growth factor (EGF) and its receptors play a role in cell proliferation and survival and are implicated in the pathobiology of pulmonary arterial hypertension (PAH). Objectives: To study the role of EGF inhibition on experimental pulmonary hypertension. Methods: We investigated (1) the effects of three clinically approved EGF receptor (EGFR) antagonists in vitro on rat pulmonary arterial smooth muscle cell proliferation and in vivo on experimental pulmonary hypertension (PH) induced by monocrotaline injection in rats and by chronic hypoxia in mice, and (2) the expression of EGFR in the lung tissues from experimental and clinical PH. Measurements and Main Results: The EGFR inhibitors gefitinib, erlotinib, and lapatinib inhibited the EGF-induced proliferation of pulmonary arterial smooth muscle cells. In rats with established PH, gefitinib and erlotinib significantly reduced right ventricular systolic pressure and right ventricular hypertrophy. In addition, the medial wall thickness and muscularization of pulmonary arteries were improved. In contrast, lapatinib did not provide therapeutic benefit. These EGFR antagonists at their highest tolerable dose did not yield significant improvement in right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in mice with chronic hypoxic PH. Moreover, no significant alteration in the EGFR expression was detected in the lung tissues from patients with idiopathic PAH. Conclusions: The partial therapeutic efficacy of the EGFR antagonists in animal models of pulmonary hypertension and the absence of significant alteration in EGFR expression in the lungs from patients with idiopathic PAH suggest that EGFRs do not represent a promising target for the treatment of pulmonary hypertension.
Abstract:
Zitierstile
Harvard-Zitierstil: Dahal, B., Cornitescu, T., Tretyn, A., Pullamsetti, S., Kosanovic, D., Dumitrascu, R., et al. (2010) Role of Epidermal Growth Factor Inhibition in Experimental Pulmonary Hypertension, American Journal of Respiratory and Critical Care Medicine, 181(2), pp. 158-167. https://doi.org/10.1164/rccm.200811-1682OC
APA-Zitierstil: Dahal, B., Cornitescu, T., Tretyn, A., Pullamsetti, S., Kosanovic, D., Dumitrascu, R., Ghofrani, H., Weissmann, N., Voswinckel, R., Banat, G., Seeger, W., Grimminger, F., & Schermuly, R. (2010). Role of Epidermal Growth Factor Inhibition in Experimental Pulmonary Hypertension. American Journal of Respiratory and Critical Care Medicine. 181(2), 158-167. https://doi.org/10.1164/rccm.200811-1682OC
Schlagwörter
BLOCKADE; cardiotoxicity; epidermal growth factor receptor; FACTOR EXPRESSION; FACTOR RECEPTOR TRANSACTIVATION; IMATINIB MESYLATE; LAPATINIB; MOLECULAR-MECHANISMS; MONOCROTALINE; Pulmonary hypertension