title: Inhibition of endocan attenuates monocrotaline-induced connective tissue disease related pulmonary arterial hypertension.
abstract: Connective tissue disease related pulmonary arterial hypertension (CTD-PAH) is characterized by vascular remodeling, endothelial dysfunction and inflammation. Endocan is a novel endothelial dysfunction marker. The aim of the present study was to investigate the role of endocan in CTD-PAH. Monocrotaline (MCT)-induced PAH rats were used as the CTD-PAH model. Short hairpin RNA packed in a lentiviral vector used to inhibit endocan expression was intratracheally instilled in rats prior to the MCT injection. Endocan was found to be increased in the serum and lung of MCT-induced PAH rats. Short hairpin RNA mediated knockdown of endocan significantly decreased right ventricular systolic pressure, attenuated pulmonary remodeling and inflammatory responses in the lung. In the in vitro study, tumor necrosis factor-α (TNF-α) exposure caused increased endocan expression in the primary cultured rat pulmonary microvascular endothelial cells (RPMECs). Endocan knockdown inhibited the permeability increase and adhesion molecules secretion in RPMECs induced by TNF-α. In addition, TNF-α induced MAPK activation was blocked when endocan gene was knocked down. These data demonstrate that endocan may play an important role in the development of CTD-PAH. This study provides novel evidence to better understand the pathogenesis of CTD-PAH, which may be beneficial for the treatment of this disease.
authors.affiliation: Department of Immunology and Rheumatology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Respiration, Liaoning Jinqiu Hospital, Shenyang 110016, People's Republic of China.
authors.forename: Yunxin
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Immunology and Rheumatology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Immunology and Rheumatology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Immunology and Rheumatology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Immunology and Rheumatology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China. Electronic address: xiaofei.wang@cstar.org.cn.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D002478:Cells, Cultured; D003238:Connective Tissue / Q000473:pathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D008297:Male; D016686:Monocrotaline; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D066253:Vascular Remodeling / Q000235:genetics
chemical_list: D011509:Proteoglycans; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; C000617036:endothelial cell-specific molecule-1, rat; D016686:Monocrotaline; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Endocan; Endothelial cells; MAPK; Pulmonary arterial hypertension; TNF-α