Adiponectin decreases pulmonary arterial remodeling in murine models of pulmonary hypertension

Meiqian Weng, Michael J. Raher, Patricio Leyton, Terry P. Combs, Philipp E. Scherer, Kenneth D. Bloch, Benjamin D. Medoff

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Remodeling of the pulmonary arteries is a common feature among the heterogeneous disorders that cause pulmonary hypertension. In these disorders, the remodeled pulmonary arteries often demonstrate inflammation and an accumulation of pulmonary artery smooth muscle cells (PASMCs) within the vessels. Adipose tissue secretes multiple bioactive mediators (adipokines) that can influence both inflammation and remodeling, suggesting that adipokines may contribute to the development of pulmonary hypertension. We recently reported on a model of pulmonary hypertension induced by vascular inflammation, in which a deficiency of the adipokine adiponectin (APN) was associated with the extensive proliferation of PASMCs and increased pulmonary artery pressures. Based on these data, we hypothesize that APN can suppress pulmonary hypertension by directly inhibiting the proliferation of PASMCs. Here, we tested the effects of APN overexpression on pulmonary arterial remodeling by using APN-overexpressing mice in a model of pulmonary hypertension induced by inflammation. Consistent with our hypothesis, mice that overexpressed APN manfiested reduced pulmonary hypertension and remodeling compared with wild-type mice, despite developing similar levels of pulmonary vascular inflammation in the model. The overexpression of APN was also protective in a hypoxic model of pulmonary hypertension. Furthermore, APN suppressed the proliferation of PASMCs, and reduced the activity of the serum response factor-serum response element pathway, which is a critical signaling pathway for smooth muscle cell proliferation. Overall, these data suggest that APN can regulate pulmonary hypertension and pulmonary arterial remodeling through its direct effects on PASMCs. Hence, the activation of APN-like activity in the pulmonary vasculature may be beneficial in pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)340-347
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume45
Issue number2
DOIs
StatePublished - Aug 1 2011

Fingerprint

Adiponectin
Pulmonary Hypertension
Pulmonary Artery
Muscle
Smooth Muscle Myocytes
Adipokines
Inflammation
Blood Vessels
Serum Response Element
Serum Response Factor
Vascular Remodeling
Cell proliferation
Critical Pathways
Adipose Tissue
Chemical activation
Pneumonia
Cells
Tissue
Cell Proliferation
Pressure

Keywords

  • Adiponectin
  • Metabolism
  • Pulmonary artery smooth muscle cells
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Adiponectin decreases pulmonary arterial remodeling in murine models of pulmonary hypertension. / Weng, Meiqian; Raher, Michael J.; Leyton, Patricio; Combs, Terry P.; Scherer, Philipp E.; Bloch, Kenneth D.; Medoff, Benjamin D.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 45, No. 2, 01.08.2011, p. 340-347.

Research output: Contribution to journalArticle

Weng, Meiqian ; Raher, Michael J. ; Leyton, Patricio ; Combs, Terry P. ; Scherer, Philipp E. ; Bloch, Kenneth D. ; Medoff, Benjamin D. / Adiponectin decreases pulmonary arterial remodeling in murine models of pulmonary hypertension. In: American Journal of Respiratory Cell and Molecular Biology. 2011 ; Vol. 45, No. 2. pp. 340-347.
@article{469e5b934d1f470d9056335bafe66865,
title = "Adiponectin decreases pulmonary arterial remodeling in murine models of pulmonary hypertension",
abstract = "Remodeling of the pulmonary arteries is a common feature among the heterogeneous disorders that cause pulmonary hypertension. In these disorders, the remodeled pulmonary arteries often demonstrate inflammation and an accumulation of pulmonary artery smooth muscle cells (PASMCs) within the vessels. Adipose tissue secretes multiple bioactive mediators (adipokines) that can influence both inflammation and remodeling, suggesting that adipokines may contribute to the development of pulmonary hypertension. We recently reported on a model of pulmonary hypertension induced by vascular inflammation, in which a deficiency of the adipokine adiponectin (APN) was associated with the extensive proliferation of PASMCs and increased pulmonary artery pressures. Based on these data, we hypothesize that APN can suppress pulmonary hypertension by directly inhibiting the proliferation of PASMCs. Here, we tested the effects of APN overexpression on pulmonary arterial remodeling by using APN-overexpressing mice in a model of pulmonary hypertension induced by inflammation. Consistent with our hypothesis, mice that overexpressed APN manfiested reduced pulmonary hypertension and remodeling compared with wild-type mice, despite developing similar levels of pulmonary vascular inflammation in the model. The overexpression of APN was also protective in a hypoxic model of pulmonary hypertension. Furthermore, APN suppressed the proliferation of PASMCs, and reduced the activity of the serum response factor-serum response element pathway, which is a critical signaling pathway for smooth muscle cell proliferation. Overall, these data suggest that APN can regulate pulmonary hypertension and pulmonary arterial remodeling through its direct effects on PASMCs. Hence, the activation of APN-like activity in the pulmonary vasculature may be beneficial in pulmonary hypertension.",
keywords = "Adiponectin, Metabolism, Pulmonary artery smooth muscle cells, Pulmonary hypertension",
author = "Meiqian Weng and Raher, {Michael J.} and Patricio Leyton and Combs, {Terry P.} and Scherer, {Philipp E.} and Bloch, {Kenneth D.} and Medoff, {Benjamin D.}",
year = "2011",
month = "8",
day = "1",
doi = "10.1165/rcmb.2010-0316OC",
language = "English (US)",
volume = "45",
pages = "340--347",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "2",

}

TY - JOUR

T1 - Adiponectin decreases pulmonary arterial remodeling in murine models of pulmonary hypertension

AU - Weng, Meiqian

AU - Raher, Michael J.

AU - Leyton, Patricio

AU - Combs, Terry P.

AU - Scherer, Philipp E.

AU - Bloch, Kenneth D.

AU - Medoff, Benjamin D.

PY - 2011/8/1

Y1 - 2011/8/1

N2 - Remodeling of the pulmonary arteries is a common feature among the heterogeneous disorders that cause pulmonary hypertension. In these disorders, the remodeled pulmonary arteries often demonstrate inflammation and an accumulation of pulmonary artery smooth muscle cells (PASMCs) within the vessels. Adipose tissue secretes multiple bioactive mediators (adipokines) that can influence both inflammation and remodeling, suggesting that adipokines may contribute to the development of pulmonary hypertension. We recently reported on a model of pulmonary hypertension induced by vascular inflammation, in which a deficiency of the adipokine adiponectin (APN) was associated with the extensive proliferation of PASMCs and increased pulmonary artery pressures. Based on these data, we hypothesize that APN can suppress pulmonary hypertension by directly inhibiting the proliferation of PASMCs. Here, we tested the effects of APN overexpression on pulmonary arterial remodeling by using APN-overexpressing mice in a model of pulmonary hypertension induced by inflammation. Consistent with our hypothesis, mice that overexpressed APN manfiested reduced pulmonary hypertension and remodeling compared with wild-type mice, despite developing similar levels of pulmonary vascular inflammation in the model. The overexpression of APN was also protective in a hypoxic model of pulmonary hypertension. Furthermore, APN suppressed the proliferation of PASMCs, and reduced the activity of the serum response factor-serum response element pathway, which is a critical signaling pathway for smooth muscle cell proliferation. Overall, these data suggest that APN can regulate pulmonary hypertension and pulmonary arterial remodeling through its direct effects on PASMCs. Hence, the activation of APN-like activity in the pulmonary vasculature may be beneficial in pulmonary hypertension.

AB - Remodeling of the pulmonary arteries is a common feature among the heterogeneous disorders that cause pulmonary hypertension. In these disorders, the remodeled pulmonary arteries often demonstrate inflammation and an accumulation of pulmonary artery smooth muscle cells (PASMCs) within the vessels. Adipose tissue secretes multiple bioactive mediators (adipokines) that can influence both inflammation and remodeling, suggesting that adipokines may contribute to the development of pulmonary hypertension. We recently reported on a model of pulmonary hypertension induced by vascular inflammation, in which a deficiency of the adipokine adiponectin (APN) was associated with the extensive proliferation of PASMCs and increased pulmonary artery pressures. Based on these data, we hypothesize that APN can suppress pulmonary hypertension by directly inhibiting the proliferation of PASMCs. Here, we tested the effects of APN overexpression on pulmonary arterial remodeling by using APN-overexpressing mice in a model of pulmonary hypertension induced by inflammation. Consistent with our hypothesis, mice that overexpressed APN manfiested reduced pulmonary hypertension and remodeling compared with wild-type mice, despite developing similar levels of pulmonary vascular inflammation in the model. The overexpression of APN was also protective in a hypoxic model of pulmonary hypertension. Furthermore, APN suppressed the proliferation of PASMCs, and reduced the activity of the serum response factor-serum response element pathway, which is a critical signaling pathway for smooth muscle cell proliferation. Overall, these data suggest that APN can regulate pulmonary hypertension and pulmonary arterial remodeling through its direct effects on PASMCs. Hence, the activation of APN-like activity in the pulmonary vasculature may be beneficial in pulmonary hypertension.

KW - Adiponectin

KW - Metabolism

KW - Pulmonary artery smooth muscle cells

KW - Pulmonary hypertension

UR - http://www.scopus.com/inward/record.url?scp=80051604395&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051604395&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2010-0316OC

DO - 10.1165/rcmb.2010-0316OC

M3 - Article

VL - 45

SP - 340

EP - 347

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 2

ER -