title: Involvement of matrix metalloproteinase-2 in medial hypertrophy of pulmonary arterioles in broiler chickens with pulmonary arterial hypertension.
abstract: Medial hypertrophy of pulmonary arterioles during pulmonary arterial hypertension (PAH) in humans is associated with enhanced proliferation of smooth muscle cells (SMCs). Elevated matrix metalloproteinase (MMP)-2 has been found in pulmonary artery SMCs (PA-SMCs) in humans with idiopathic PAH, leading to the hypothesis that MMP-2 contributes to the proliferation and migration of vascular SMCs in the pathogenesis of PAH. Rapidly growing meat-type (broiler) chickens provide a model of spontaneous PAH. The present study was conducted to determine whether MMP-2 is involved in the medial hypertrophy of pulmonary arterioles in this model. Cultured PA-SMCs from normal birds were used to evaluate the effect of MMPs on cell proliferation. Gelatin zymography showed that endothelin (ET)-1-induced proliferation of PA-SMCs was concomitant with increased pro- and active MMP-2 production. Reverse transcription PCR demonstrated upregulation of MMP-2 mRNA. However, PA-SMC proliferation was inhibited by the MMP inhibitors doxycycline and cis-9-octadecenoyl-N-hydroxylamide. In vivo experiments revealed a significant increase of MMP-2 expression in hypertrophied pulmonary arterioles of PAH broiler chickens, which was positively correlated with wall thickness and medial hypertrophy. MMP-2 may contribute to medial hypertrophy in pulmonary arterioles during PAH in broiler chickens by enhancing the proliferation of vascular SMCs.
authors.affiliation: Key Laboratory of Animal Virology of Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China. tanxun@zju.edu.cn
authors.forename: Xun
authors.initials: X
authors.lastname: Tan
authors.forename: Juan
authors.initials: J
authors.lastname: Chai
authors.forename: Shi-Cheng
authors.initials: SC
authors.lastname: Bi
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Li
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Li
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000473:pathology; D002645:Chickens; D004318:Doxycycline / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel / Q000662:veterinary; D019332:Endothelin-1 / Q000378:metabolism; D065627:Familial Primary Pulmonary Hypertension; D015971:Gene Expression Regulation, Enzymologic; D006877:Hydroxamic Acids / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000201:enzymology / Q000662:veterinary*; D006984:Hypertrophy / Q000139:chemically induced / Q000201:enzymology / Q000662:veterinary*; D008168:Lung / Q000098:blood supply* / Q000166:cytology / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D011201:Poultry Diseases / Q000139:chemically induced / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; C474031:N-hydroxy-9-octadecenamide; D012965:Sodium Chloride; D020778:Matrix Metalloproteinase 2; D004318:Doxycycline