title: Association between endothelial function and micro-vascular remodeling measured by synchrotron radiation pulmonary micro-angiography in pulmonary arterial hypertension.
abstract: OBJECTIVE
  Pulmonary arterial hypertension (PAH) is a progressive disease which causes increased vascular resistance. In this study, our purpose was to quantify the micro-vascular remodeling in monocrotaline-induced PAH rats using synchrotron radiation pulmonary micro-angiography (SRPA), a method we have previously established in an in vivo rat model. To determine the relationship between endothelial function and vascular remodeling, the local expression of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) was evaluated using immunohistochemical staining.
  
  
  METHODS
  Monocrotaline-induced PAH rats were created by subcutaneous injection of monocrotaline. After 2 weeks, SRPA was performed at the Photon Factory of the High Energy Accelerator Research Organization. The internal diameters of pulmonary arterioles were measured using SRPA images. Semi-quantified analyses of ET-1, eNOS and VEGF expression in pulmonary arterioles were performed by immunohistochemical staining.
  
  
  RESULTS
  Micro-vascular density and the internal diameters of pulmonary arterioles were significantly decreased in PAH. ET-1 expression was significantly increased in PAH compared with the control (1.53 ± 0.45 vs. 0.80 ± 0.14) and eNOS expression was significantly decreased in PAH compared with the control (1.12 ± 0.59 vs. 1.91 ± 0.66), although VEGF expression did not differ between the groups.
  
  
  CONCLUSIONS
  SRPA can be effectively used for visualizing the decreased pulmonary micro-vasculature associated with PAH. Increased ET-1 expression and decreased eNOS expression may contribute to the proliferation and vasospasm of pulmonary arterioles induced by endothelial dysfunction due to PAH. This SRPA technology may help to identify a correlation between endothelial function and micro-vasculature remodeling in PAH.
authors.affiliation: School of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Fuji
authors.affiliation: Department of Health Science, Tsukuba University of Technology, Tsukuba, Japan.
authors.forename: Shonosuke
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: Photon Factory, High Energy Accelerator Research Organization, Tsukuba, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hyodo
authors.affiliation: Department of Cardiovascular Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8577, Japan.
authors.forename: Motoo
authors.initials: M
authors.lastname: Osaka
authors.affiliation: Department of Cardiovascular Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8577, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Tokyo Denki University, Tsukuba, Japan.
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Tanioka
authors.affiliation: NHK Science and Technology Research Laboratories, Tsukuba, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Miyakawa
authors.affiliation: NHK Science and Technology Research Laboratories, Tsukuba, Japan.
authors.forename: Misao
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Department of Cardiovascular Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8577, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hiramatsu
authors.affiliation: Department of Cardiovascular Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8577, Japan. chiho-t@md.tsukuba.ac.jp.
authors.forename: Chiho
authors.identifier: http://orcid.org/0000-0002-1349-4148
authors.initials: C
authors.lastname: Tokunaga
mesh_terms: D000792:Angiography / Q000379:methods; D000818:Animals; D062186:Arterial Pressure / Q000502:physiology; D001160:Arterioles / Q000000981:diagnostic imaging / Q000473:pathology; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006984:Hypertrophy; D008168:Lung / Q000098:blood supply; D008297:Male; D016686:Monocrotaline; D052250:Nitric Oxide Synthase Type III; D011651:Pulmonary Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017356:Synchrotrons; D013927:Thrombosis / Q000209:etiology; D042461:Vascular Endothelial Growth Factor A; D066253:Vascular Remodeling / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016686:Monocrotaline; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Micro-vascular remodeling; Pulmonary artery hypertension; Synchrotron radiation