Bone marrow-derived cells contribute to pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension

Kentaro Hayashida, Jun Fujita, Yoshiko Miyake, Hiroshi Kawada, Kiyoshi Ando, Satoshi Ogawa, Keiichi Fukuda

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Study objective: In these days, it was reported that bone marrow (BM) cells might take part in the remodeling of some systemic vascular diseases; however, it remains unknown whether the BM cells were involved in the vascular remodeling of pulmonary arteries and the progression of pulmonary hypertension (PH). The purpose of this study was to investigate whether BM-derived cells contribute to pulmonary vascular remodeling in hypoxia-induced PH. Materials and methods: To investigate the role of BM-derived cells, we transplanted the whole BM of enhanced green fluorescent protein (GFP)-transgenic mice to the lethally irradiated syngeneic mice (n = 30). After 8 weeks, chimera mice were exposed to consistent hypoxia using a hypoxic chamber (10% O2) for up to 4 or 8 weeks (10 mice per group). After hemodynamics and the ratio of right ventricular (RV) weight to left ventricle (LV) weight, RV/(LV + septum [S]), were measured, histologic and immunofluorescent staining were performed. Results: BM-transplanted mice showed a high chimerism (mean [± SEM], 91 ± 2.3%). RV systolic pressure and the RV/(LV + S) ratio increased significantly with time in PH mice, indicating RV hypertrophy. Marked vascular remodeling including medial hypertrophy and adventitial proliferation was observed in the pulmonary arteries of PH mice. Strikingly, a number of GFP+ cells were observed at the pulmonary arterial wall, including the adventitia, in hypoxia-induced PH mice, while very few cells were observed in the control mice. Metaspectrometer measurements using confocal laser scanning microscopy confirmed that this green fluorescence was produced by GFP, suggesting that these GFP+ cells were mobilized from the BM. Most of them expressed α-smooth muscle actin, a smooth muscle cell, or myofibroblast phenotype, and contributed to the pulmonary vascular remodeling. A semiquantitative polymerase chain reaction of the GFP gene revealed that the BM-derived GFP-positive cells in the PH group were observed more than eightfold as often compared with the control mice. Conclusion: The BM-derived cells mobilize to the hypertensive pulmonary arteries and contribute to the pulmonary vascular remodeling in hypoxia-induced PH mice.

Original languageEnglish
Pages (from-to)1793-1798
Number of pages6
JournalChest
Volume127
Issue number5
DOIs
Publication statusPublished - 2005 May

Fingerprint

Pulmonary Hypertension
Bone Marrow Cells
Lung
Green Fluorescent Proteins
Bone Marrow
Pulmonary Artery
Heart Ventricles
Adventitia
Hypoxia
Vascular Remodeling
Right Ventricular Hypertrophy
Weights and Measures
Chimerism
Myofibroblasts
Ventricular Pressure
Vascular Diseases
Confocal Microscopy
Hypertrophy
Transgenic Mice
Smooth Muscle Myocytes

Keywords

  • Bone marrow transplantation
  • Hypoxia
  • Myofibroblast
  • Progenitor cell
  • Pulmonary hypertension
  • Vascular remodeling

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Bone marrow-derived cells contribute to pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension. / Hayashida, Kentaro; Fujita, Jun; Miyake, Yoshiko; Kawada, Hiroshi; Ando, Kiyoshi; Ogawa, Satoshi; Fukuda, Keiichi.

In: Chest, Vol. 127, No. 5, 05.2005, p. 1793-1798.

Research output: Contribution to journalArticle

Hayashida, Kentaro ; Fujita, Jun ; Miyake, Yoshiko ; Kawada, Hiroshi ; Ando, Kiyoshi ; Ogawa, Satoshi ; Fukuda, Keiichi. / Bone marrow-derived cells contribute to pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension. In: Chest. 2005 ; Vol. 127, No. 5. pp. 1793-1798.
@article{72a48ce33367440a8fc54a1c2b39523e,
title = "Bone marrow-derived cells contribute to pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension",
abstract = "Study objective: In these days, it was reported that bone marrow (BM) cells might take part in the remodeling of some systemic vascular diseases; however, it remains unknown whether the BM cells were involved in the vascular remodeling of pulmonary arteries and the progression of pulmonary hypertension (PH). The purpose of this study was to investigate whether BM-derived cells contribute to pulmonary vascular remodeling in hypoxia-induced PH. Materials and methods: To investigate the role of BM-derived cells, we transplanted the whole BM of enhanced green fluorescent protein (GFP)-transgenic mice to the lethally irradiated syngeneic mice (n = 30). After 8 weeks, chimera mice were exposed to consistent hypoxia using a hypoxic chamber (10{\%} O2) for up to 4 or 8 weeks (10 mice per group). After hemodynamics and the ratio of right ventricular (RV) weight to left ventricle (LV) weight, RV/(LV + septum [S]), were measured, histologic and immunofluorescent staining were performed. Results: BM-transplanted mice showed a high chimerism (mean [± SEM], 91 ± 2.3{\%}). RV systolic pressure and the RV/(LV + S) ratio increased significantly with time in PH mice, indicating RV hypertrophy. Marked vascular remodeling including medial hypertrophy and adventitial proliferation was observed in the pulmonary arteries of PH mice. Strikingly, a number of GFP+ cells were observed at the pulmonary arterial wall, including the adventitia, in hypoxia-induced PH mice, while very few cells were observed in the control mice. Metaspectrometer measurements using confocal laser scanning microscopy confirmed that this green fluorescence was produced by GFP, suggesting that these GFP+ cells were mobilized from the BM. Most of them expressed α-smooth muscle actin, a smooth muscle cell, or myofibroblast phenotype, and contributed to the pulmonary vascular remodeling. A semiquantitative polymerase chain reaction of the GFP gene revealed that the BM-derived GFP-positive cells in the PH group were observed more than eightfold as often compared with the control mice. Conclusion: The BM-derived cells mobilize to the hypertensive pulmonary arteries and contribute to the pulmonary vascular remodeling in hypoxia-induced PH mice.",
keywords = "Bone marrow transplantation, Hypoxia, Myofibroblast, Progenitor cell, Pulmonary hypertension, Vascular remodeling",
author = "Kentaro Hayashida and Jun Fujita and Yoshiko Miyake and Hiroshi Kawada and Kiyoshi Ando and Satoshi Ogawa and Keiichi Fukuda",
year = "2005",
month = "5",
doi = "10.1378/chest.127.5.1793",
language = "English",
volume = "127",
pages = "1793--1798",
journal = "Chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "5",

}

TY - JOUR

T1 - Bone marrow-derived cells contribute to pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension

AU - Hayashida, Kentaro

AU - Fujita, Jun

AU - Miyake, Yoshiko

AU - Kawada, Hiroshi

AU - Ando, Kiyoshi

AU - Ogawa, Satoshi

AU - Fukuda, Keiichi

PY - 2005/5

Y1 - 2005/5

N2 - Study objective: In these days, it was reported that bone marrow (BM) cells might take part in the remodeling of some systemic vascular diseases; however, it remains unknown whether the BM cells were involved in the vascular remodeling of pulmonary arteries and the progression of pulmonary hypertension (PH). The purpose of this study was to investigate whether BM-derived cells contribute to pulmonary vascular remodeling in hypoxia-induced PH. Materials and methods: To investigate the role of BM-derived cells, we transplanted the whole BM of enhanced green fluorescent protein (GFP)-transgenic mice to the lethally irradiated syngeneic mice (n = 30). After 8 weeks, chimera mice were exposed to consistent hypoxia using a hypoxic chamber (10% O2) for up to 4 or 8 weeks (10 mice per group). After hemodynamics and the ratio of right ventricular (RV) weight to left ventricle (LV) weight, RV/(LV + septum [S]), were measured, histologic and immunofluorescent staining were performed. Results: BM-transplanted mice showed a high chimerism (mean [± SEM], 91 ± 2.3%). RV systolic pressure and the RV/(LV + S) ratio increased significantly with time in PH mice, indicating RV hypertrophy. Marked vascular remodeling including medial hypertrophy and adventitial proliferation was observed in the pulmonary arteries of PH mice. Strikingly, a number of GFP+ cells were observed at the pulmonary arterial wall, including the adventitia, in hypoxia-induced PH mice, while very few cells were observed in the control mice. Metaspectrometer measurements using confocal laser scanning microscopy confirmed that this green fluorescence was produced by GFP, suggesting that these GFP+ cells were mobilized from the BM. Most of them expressed α-smooth muscle actin, a smooth muscle cell, or myofibroblast phenotype, and contributed to the pulmonary vascular remodeling. A semiquantitative polymerase chain reaction of the GFP gene revealed that the BM-derived GFP-positive cells in the PH group were observed more than eightfold as often compared with the control mice. Conclusion: The BM-derived cells mobilize to the hypertensive pulmonary arteries and contribute to the pulmonary vascular remodeling in hypoxia-induced PH mice.

AB - Study objective: In these days, it was reported that bone marrow (BM) cells might take part in the remodeling of some systemic vascular diseases; however, it remains unknown whether the BM cells were involved in the vascular remodeling of pulmonary arteries and the progression of pulmonary hypertension (PH). The purpose of this study was to investigate whether BM-derived cells contribute to pulmonary vascular remodeling in hypoxia-induced PH. Materials and methods: To investigate the role of BM-derived cells, we transplanted the whole BM of enhanced green fluorescent protein (GFP)-transgenic mice to the lethally irradiated syngeneic mice (n = 30). After 8 weeks, chimera mice were exposed to consistent hypoxia using a hypoxic chamber (10% O2) for up to 4 or 8 weeks (10 mice per group). After hemodynamics and the ratio of right ventricular (RV) weight to left ventricle (LV) weight, RV/(LV + septum [S]), were measured, histologic and immunofluorescent staining were performed. Results: BM-transplanted mice showed a high chimerism (mean [± SEM], 91 ± 2.3%). RV systolic pressure and the RV/(LV + S) ratio increased significantly with time in PH mice, indicating RV hypertrophy. Marked vascular remodeling including medial hypertrophy and adventitial proliferation was observed in the pulmonary arteries of PH mice. Strikingly, a number of GFP+ cells were observed at the pulmonary arterial wall, including the adventitia, in hypoxia-induced PH mice, while very few cells were observed in the control mice. Metaspectrometer measurements using confocal laser scanning microscopy confirmed that this green fluorescence was produced by GFP, suggesting that these GFP+ cells were mobilized from the BM. Most of them expressed α-smooth muscle actin, a smooth muscle cell, or myofibroblast phenotype, and contributed to the pulmonary vascular remodeling. A semiquantitative polymerase chain reaction of the GFP gene revealed that the BM-derived GFP-positive cells in the PH group were observed more than eightfold as often compared with the control mice. Conclusion: The BM-derived cells mobilize to the hypertensive pulmonary arteries and contribute to the pulmonary vascular remodeling in hypoxia-induced PH mice.

KW - Bone marrow transplantation

KW - Hypoxia

KW - Myofibroblast

KW - Progenitor cell

KW - Pulmonary hypertension

KW - Vascular remodeling

UR - http://www.scopus.com/inward/record.url?scp=19844374754&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19844374754&partnerID=8YFLogxK

U2 - 10.1378/chest.127.5.1793

DO - 10.1378/chest.127.5.1793

M3 - Article

C2 - 15888860

AN - SCOPUS:19844374754

VL - 127

SP - 1793

EP - 1798

JO - Chest

JF - Chest

SN - 0012-3692

IS - 5

ER -