title: Arginase inhibition protects against hypoxia‑induced pulmonary arterial hypertension.
abstract: The present study aimed to determine the role of arginase (Arg) in pulmonary arterial hypertension (PAH). In vitro, human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic conditions with, or without, the Arg inhibitor, S‑(2‑boronoethyl)‑l‑cysteine (BEC), for 48 h, following which the proliferation of the HPASMCs was determined using MTT and cell counting assays. For the in vivo investigation, 30 male rats were randomly divided into the following three groups (n=10 per group): i) control group, ii) PAH group and iii) BEC group, in which the right ventricle systolic pressure (RVSP) of the rats was assessed. The levels of cyclin D1, cyclin‑dependent kinase (CDK)4 and p27 were measured in vitro and in vivo. The phosphorylation levels of Akt and extracellular‑related kinase (ERK) were also measured in HPASMCs. In vitro, compared with the hypoxia group, Arg inhibition reduced HPASMC proliferation and reduced the expression levels of cyclin D1, CDK4, phosphorylated (p‑)Akt and p‑ERK. By contrast, Arg inhibition increased the expression of p27. In vivo, compared with the control group, the expression levels of cyclin D1 and CDK4 were reduced in the PAH group, however, the expression of p27 and the RVSP increased. In the BEC group, the opposite effects were observed. Therefore, it was suggested that Arg inhibition may reduce the RVSP of PAH rats and reduce HPASMC proliferation by decreasing the expression levels of cyclin D1 and CDK4, increasing the expression of p27, and partly reducing the phosphorylation of Akt and ERK.
authors.affiliation: Department of Interventional Radiology, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Interventional Radiology, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Bolin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Interventional Radiology, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Xuepeng
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Interventional Radiology, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Interventional Radiology, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Ligang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Interventional Radiology, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Interventional Radiology, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001897:Boronic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology; D011651:Pulmonary Artery / Q000473:pathology; D017207:Rats, Sprague-Dawley; D017725:Ventricular Pressure
chemical_list: C425062:(2-boronoethyl)-cysteine; D001897:Boronic Acids; C530104:CCND1 protein, human; C436291:CDKN1B protein, human; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D001119:Arginase