Adventitial fibroblast Nox4 expression and ROS signaling in pulmonary arterial hypertension

Research output: Chapter in Book/Report/Conference proceedingChapter

7 Citations (Scopus)

Abstract

Pulmonary arterial hypertension (PAH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PA) resulting in high pulmonary arterial blood pressure and ultimately right ventricular failure. Elevated production of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4), a constitutively active enzyme, has been associated with oxygen sensing, vasomotor control, cellular proliferation, differentiation, migration, apoptosis, senescence, fibrosis, and angiogenesis. Further, elevated expression of Nox4 has been reported in a number of cardiovascular diseases, including atherosclerosis, hypertension, cardiac failure, ischemic stroke, and PAH. However, the cellular location of Nox4 and its contribution to aberrant vascular remodeling in PAH remains poorly understood. The goal of this review is to summarize the recent literature on the enzymatic regulation of Nox4 in the production of ROS in PAH. In the vascular wall, Nox4 is present in fibroblasts, a primary cell of the adventitia, and matches the adventitial location of ROS production in PAH. Further, in adventitial fibroblasts, Nox4 overexpression stimulates migration and proliferation as well as matrix gene expression. Collectively, reports indicate that Nox4 contributes to altered fibroblast behavior, ROS production leading to hypertensive vascular remodeling and the development of PAH. Finally, we address the functional significance of Nox4 in fibroblasts, and also suggest an “outside in” (adventitial) process of vascular remodeling that is mediated by Nox4, which although has physiological roles in the intimal layer (i.e., endothelium), may also have pathologic importance in the adventitial layer of the vascular wall through signaling in fibroblasts.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages1-11
Number of pages11
DOIs
StatePublished - Jan 1 2017

Publication series

NameAdvances in Experimental Medicine and Biology
Volume967
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Fingerprint

Adventitia
NADPH Oxidase
Fibroblasts
Pulmonary Hypertension
Reactive Oxygen Species
Blood Vessels
Tunica Intima
Blood pressure
Gene expression
Pulmonary Artery
Endothelium
Atherosclerosis
Arterial Pressure
Fibrosis
Cardiovascular Diseases
Heart Failure
Stroke
Cell Proliferation
Apoptosis
Oxygen

Keywords

  • Adventitia
  • Nox4
  • Pulmonary
  • ROS signaling
  • Vascular remodeling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Barman, S. A., & Fulton, D. J. (2017). Adventitial fibroblast Nox4 expression and ROS signaling in pulmonary arterial hypertension. In Advances in Experimental Medicine and Biology (pp. 1-11). (Advances in Experimental Medicine and Biology; Vol. 967). Springer New York LLC. https://doi.org/10.1007/978-3-319-63245-2_1

Adventitial fibroblast Nox4 expression and ROS signaling in pulmonary arterial hypertension. / Barman, Scott A; Fulton, David J.

Advances in Experimental Medicine and Biology. Springer New York LLC, 2017. p. 1-11 (Advances in Experimental Medicine and Biology; Vol. 967).

Research output: Chapter in Book/Report/Conference proceedingChapter

Barman, SA & Fulton, DJ 2017, Adventitial fibroblast Nox4 expression and ROS signaling in pulmonary arterial hypertension. in Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology, vol. 967, Springer New York LLC, pp. 1-11. https://doi.org/10.1007/978-3-319-63245-2_1
Barman SA, Fulton DJ. Adventitial fibroblast Nox4 expression and ROS signaling in pulmonary arterial hypertension. In Advances in Experimental Medicine and Biology. Springer New York LLC. 2017. p. 1-11. (Advances in Experimental Medicine and Biology). https://doi.org/10.1007/978-3-319-63245-2_1
Barman, Scott A ; Fulton, David J. / Adventitial fibroblast Nox4 expression and ROS signaling in pulmonary arterial hypertension. Advances in Experimental Medicine and Biology. Springer New York LLC, 2017. pp. 1-11 (Advances in Experimental Medicine and Biology).
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