Endothelin-Induced Collagen Remodeling in Experimental Pulmonary Hypertension

• Published in: Biochemical and biophysical research communications Vol. 215; no. 3; pp. 981 - 986
• Main Authors: Mansoor, A.M., Honda, M., Saida, K., Ishinaga, Y., Kuramochi, T., Maeda, A., Takabatake, T., Mitsui, Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.10.1995
• Subjects: Animals; Collagen - analysis; Collagen - metabolism; Collagen - physiology; Endothelins - analysis; Endothelins - biosynthesis; Endothelins - physiology; Gene Expression; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - pathology; Hypertrophy, Left Ventricular - pathology; Hypertrophy, Left Ventricular - physiopathology; Lung - metabolism; Lung - pathology; Male; Monocrotaline; Rats; Rats, Sprague-Dawley; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Time Factors
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1995.2560

To investigate pathophysiological roles of endothelin-1 (ET-1) in collagen remodeling in pulmonary hypertension, we measured: (a) mRNA expression, concentration, localization of ET-1; (b) changes in types and content of collagen in the lung; (c) and confirmed direct effects of ET-1 on type V collagen metabolism in vascular smooth muscle cells. Monocrotaline-treated rats showed pulmonary hypertension with medial hypertrophy and perivascular fibrosis of pulmonary arteries. At the progressive stage of pulmonary hypertension, both ET-1 levels and its mRNA expression in the lung increased. Total collagen in the lung rose markedly with a higher rate of increase in type V collagen. ET-1, which exists in vascular smooth muscle cells, other perivascular cells and endothelium, stimulated type V collagen production. Our results suggest that local production of ET-1 in the lung contributes to progression of pulmonary hypertension through changes in phenotypes and content of collagen.