Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 45, Issue 3, Pages 329-335Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2008.04.024
Keywords
NADPH oxidase; reactive oxygen species; Nox5; vascular smooth muscle cells; proliferation
Funding
- NHLBI NIH HHS [HL074604, F32 HL074604, F32 HL074604-02, R01 HL058863, R01 HL058863-10, HL058863] Funding Source: Medline
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The proliferation of vascular smooth muscle cells is important in the pathogenesis of many vascular diseases. Reactive oxygen species (ROS) produced by NADPH oxidases in smooth muscle cells have been shown to participate in signaling cascades regulating proliferation induced by platelet-derived growth factor (PDGF), a powerful smooth muscle mitogen. We sought to determine the role of Nox5 in the regulation of PDGF-stimulated human aortic smooth muscle cell (HASMC) proliferation. Cultured HASMC were found to express four isoforms of Nox5. When HASMC stimulated with PDGF were pretreated with N-acetyl cysteine (NAC), proliferation was significantly reduced. Proliferation induced by PDGF was also heavily dependent on JAK/STAT activation, as the JAK inhibitor, AG490, was able to completely abolish PDGF-stimulated HASIVIC growth. Specific knockdown of Nox5 with a siRNA strategy reduced PDGF-induced HASMC ROS production and proliferation. Additionally, siRNA to Nox5 inhibited PDGF-stimulated JAK2 and STAT3 phosphorylation. ROS produced by Nox5 play an important role in PDGF-induced JAK/STAT activation and HASIVIC proliferation. (c) 2008 Elsevier Inc. All rights reserved.
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