title: Functional Improvement and Regression of Medial Hypertrophy in the Remodeled Pulmonary Artery after Correction of Systemic Left-to-Right Shunt.
abstract: The presence of systemic left-to-right shunt and increased pulmonary blood flow can result in right heart failure and pulmonary arteriopathy. Correction of left-to-right shunt has been shown to improve cardiac function and physical performance. However, the cardiopulmonary remodeling processes following cessation of left-to-right shunt have yet to be reported. In this experimental study, excessive pulmonary flow was restored through ligation of the aortocaval fistula in rats with flow-induced pulmonary hypertension. The cardiopulmonary morphometric functions were assessed, and phenotypic switching of pulmonary vascular smooth muscle cells (VSMC) was determined. Ligation of aortocaval fistula significantly attenuated pulmonary blood flow and right ventricular mass, and potentiated the isometric contraction of pulmonary artery. Inflammatory cytokines IL-1β and IL-6 were reduced in the lung after ligation. Reduction of pulmonary blood flow restored the expressions of smooth muscle myosin heavy chain and α-smooth muscle actin in pulmonary artery, indicating the switching of VSMCs to the contractile phenotype. Our study demonstrated that normalization of pulmonary blood flow in flow-induced pulmonary hypertension reverses the remodeling in the right ventricle and pulmonary artery. The remodeling process of flow-induced pulmonary hypertension is functionally and morphometrically reversible by inducing transdifferentiation of pulmonary VSMC to contractile phenotypes and modulation of tissue inflammatory cytokines.
authors.affiliation: Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.|Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.|Division of Cardiovascular Surgery Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.
authors.forename: Jun-Neng
authors.initials: JN
authors.lastname: Roan
authors.affiliation: Department of Internal Medicine, China Medical University, 95 Xueshi Road, Taichung City 40454, Taiwan.
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Buddhist Tzu-Chi General Hospital and Tzu-Chi University School of Medicine, 707 Zhongyang Road Section 3, Hualien City 970, Taiwan.|Department of Anesthesiology, Taipei Medical University Hospital and School of Medicine, College of Medicine, Taipei Medical University, 252 Wu-Xing Street, Taipei 110, Taiwan.
authors.forename: Chen-Fuh
authors.initials: CF
authors.lastname: Lam
mesh_terms: D000818:Animals; D001159:Arterio-Arterial Fistula / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004452:Echocardiography; D006984:Hypertrophy; D018836:Inflammation Mediators / Q000378:metabolism; D007537:Isometric Contraction; D008026:Ligation; D008168:Lung / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010641:Phenotype; D011651:Pulmonary Artery / Q000002:abnormalities / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D058017:Vascular Grafting / Q000379:methods*; D066253:Vascular Remodeling; D014666:Vasomotor System / Q000503:physiopathology; D016278:Ventricular Function, Right / Q000502:physiology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators