title: Rosuvastatin alleviates the development of monocrotaline-induced pulmonary hypertension in rats.
abstract: Statins can increase endothelial function through enhancement of the expression and activity of endothelial nitric oxide synthase (eNOS). The aim of this study is to evaluate the effect of rosuvastatin on the number of circulating endothelial progenitor cells (EPCs) and endothelial expression of eNOS in monocrotaline-induced pulmonary hypertensive rats. Sixty Sprague-Dawley (SD) rats were divided into three groups of 20: control (group A), pulmonary hypertension (PAH) + rosuvastatin group (group B), and PAH (group C). Monocrotaline (MCT; 60 mg/kg) was injected (intraperitoneally) to induce PAH. Rats in group B received rosuvastatin [10 mg/(kg. day)] for 2 weeks. Peripheral blood (5 mL) was aspirated from the femoral artery of each rat before and after 2 weeks of treatment. Mononuclear cells were isolated and subcultured to obtain EPCs. Small and moderately sized pulmonary arteries were collected 2 weeks later for histological analyses. eNOS gene expression in endothelial cells of pulmonary arteries were then determined at mRNA and protein levels. eNOS expression at mRNA and protein levels and the number of circulating EPCs were reduced significantly in groups B and C compared with group A (P less than 0.05), and a significant difference between group B and group C (P less than 0.05) was observed. Vascular remodeling in small and moderately sized pulmonary arteries was attenuated markedly in group B compared with group C. These results suggest that rosuvastatin can ameliorate the remodeling of pulmonary arteries in MCT-induced PAH rats by increasing the number of circulating EPCs and eNOS upregulation.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Biological Science, The Pennsylvania State University, Pennsylvania State, USA.
authors.forename: T X
authors.initials: TX
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.
authors.forename: N
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.
authors.forename: D L
authors.initials: DL
authors.lastname: Shen
mesh_terms: D000818:Animals; D001160:Arterioles / Q000473:pathology; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000201:enzymology; D004730:Endothelium, Vascular / Q000503:physiopathology; D004790:Enzyme Induction / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis* / Q000235:genetics; D011651:Pulmonary Artery / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*; D017540:Tunica Media / Q000648:ultrastructure; D015854:Up-Regulation / Q000187:drug effects; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D012333:RNA, Messenger; D016686:Monocrotaline; D000068718:Rosuvastatin Calcium; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat