title: Salusin-β contributes to vascular inflammation associated with pulmonary arterial hypertension in rats.
abstract: Inflammation is closely linked to pulmonary arterial hypertension (PAH). Salusin-β, a bioactive peptide, has been reported to participate in vascular inflammation. We therefore hypothesized that salusin-β contributes to monocrotaline (MCT)-induced PAH in rats.
  
  
  
  Male Sprague-Dawley rats were treated with MCT (60 mg kg(-1), single intraperitoneal injection). Salusin-β expression in the lungs of the MCT-treated rats was evaluated using immunofluorescence staining, western blot, and real-time PCR. For salusin-β blockade assay, rats injected with MCT were given a chronic infusion of anti-salusin-β immunoglobulin G (IgG) (salusin-β blocker, 1.0 μg kg(-1) h(-1)) or isotype-matched control IgG. Four weeks after MCT+anti-salusin-β treatment, the effects of salusin-β blockade were determined using hemodynamics, western blot, real-time PCR, and immunohistochemical detection. The effect of salusin-β on human pulmonary arterial endothelial cell (HPAEC) function was detected by adhesion and tube formation experiments in vitro.
  
  
  
  Salusin-β expression was significantly increased in the lungs of the MCT-treated rats, and immunofluorescence results showed that salusin-β was predominantly expressed in pulmonary macrophages and vascular endothelial cells. Salusin-β blockade significantly ameliorated PAH by acting against pulmonary vascular remodeling, decreasing macrophage infiltration, and reducing pro-inflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity in the lungs of the MCT-treated rats. In addition, salusin-β could induce cell adhesion and accelerate angiogenesis by activating the NF-κB pathway and promoting pro-inflammatory cytokine expression in the cultured HPAECs. This effect was suppressed by addition of the NF-κB inhibitor, N-acetyl-L-cysteine.
  
  
  
  Salusin-β plays a crucial role in the development of MCT-induced PAH models.
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University School of Basic Medical Sciences, Beijing, People's Republic of China; Central Laboratory, Jinzhou Medical University, Jinzhou, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University School of Basic Medical Sciences, Beijing, People's Republic of China. Electronic address: zhifeiz@ccmu.edu.cn.
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University School of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University School of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University School of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University School of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: Wang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University School of Basic Medical Sciences, Beijing, People's Republic of China. Electronic address: wang_jun@ccmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000494:pharmacology; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D016686:Monocrotaline; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; C528274:salusin-beta, rat; D016686:Monocrotaline
keywords: NF-κB; monocrotaline; pulmonary arterial hypertension; salusin-β