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(Circulation Research. 2006;98:1465.)
© 2006 American Heart Association, Inc.

Editorials

TRPC Channel Upregulation in Chronically Hypoxic Pulmonary Arteries

The HIF-1 Bandwagon Gathers Steam

Philip I. Aaronson

From King’s College London, Division of Asthma, Allergy, and Lung Biology, School of Medicine, London, UK.

Correspondence to Philip I Aaronson, Room 2:20, New Hunt’s House, Guy’s Hospital campus, King’s College London, London SE1 1UL, UK. E-mail philip.aaronson@kcl.ac.uk

See related article, pages 1528–1537

Key Words: TRP channels • hypoxia-inducible factor • HIF-1 • chronic hypoxia • pulmonary arteries • pulmonary hypertension

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Chronic alveolar hypoxia causes structural and functional changes in pulmonary arteries (PAs) leading to increased pulmonary vascular resistance, secondary pulmonary hypertension (SPH), and, as a possible consequence, right heart failure. These changes are likely to result, at least in part, from the altered expression of ion channels in pulmonary arterial smooth muscle cells (PASMCs), and recent reports indicate that an increase in the expression of TRPC (canonical transient receptor potential) channels in these cells may play an important role. What has not been evident, however, is the mechanism by which chronic hypoxia (CH) enhances TRPC channel expression in these cells. In this issue of Circulation Research, Wang and colleagues¹ now elegantly demonstrate that an increased expression of TRPC1 and TRPC6 in PASMCs during CH in mice and rats is mediated by the ubiquitous oxygen-sensitive transcription factor hypoxia-inducible factor 1 (HIF-1).

	Effects of Chronic Hypoxia on Pulmonary Arteries: A Role for TRPC Channels

 
Prolonged exposure of the pulmonary vasculature to hypoxia evokes structural alterations including hypertrophy and hyperplasia of PASMCs leading to thickening of PA and neomuscularization of pulmonary arterioles. At the same time, pulmonary vascular reactivity is generally increased; basal tone rises, as does agonist-stimulated vasoconstriction, whereas endothelium-dependent dilation diminishes.² Conversely, CH depresses PA constriction elicited by acute hypoxia (hypoxic pulmonary vasoconstriction).³

On a cellular level, CH causes PASMC membrane depolarization associated with a reduced expression and function of voltage-gated K⁺ channels.^4,5 This has been proposed to contribute to PASMC proliferation by causing a rise in [K⁺]_i and inhibiting apoptosis.⁶ A rise in the basal [Ca²⁺]_i of PASMC has . . . [Full Text of this Article]

Related Article:

Hypoxia Inducible Factor 1 Mediates Hypoxia-Induced TRPC Expression and Elevated Intracellular Ca²⁺ in Pulmonary Arterial Smooth Muscle Cells

Jian Wang, Letitia Weigand, Wenju Lu, J.T. Sylvester, Gregg L. Semenza, and Larissa A. Shimoda
Circ. Res. 2006 98: 1528-1537. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				W. Wu, O. Platoshyn, A. L. Firth, and J. X.-J. Yuan Hypoxia divergently regulates production of reactive oxygen species in human pulmonary and coronary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L952 - L959. [Abstract] [Full Text] [PDF]