Endothelin induced collagen remodeling in experimental pulmonary hypertension.
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.
D000818:Animals; D003094:Collagen / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D016232:Endothelins / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology*; D015870:Gene Expression; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D016686:Monocrotaline; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016232:Endothelins; D012333:RNA, Messenger; D016686:Monocrotaline; D003094:Collagen