期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 44, 期 7, 页码 1232-1245出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2007.12.025
关键词
smooth muscle; nitric oxide; iNOS; superoxide; NADPH oxidase; protein kinase C; MAP kinase; NF-kappa B; free radicals
资金
- NCI NIH HHS [CA-89366, R01 CA089366-05, R01 CA089366, R01 CA089366-03, R01 CA089366-02, R01 CA089366-04] Funding Source: Medline
- NHLBI NIH HHS [R01 HL049426-15, R01-HL-40992, T32 HL007194, T-32-HL-07194, R01-HL-49426, R01 HL040992-13, R01 HL049426, T32 HL007194-26] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA089366] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL040992, R01HL049426, T32HL007194] Funding Source: NIH RePORTER
Inflammation plays a critical role in promoting smooth muscle migration and proliferation during vascular diseases such as postangioplasty restenosis and atherosclerosis. Another common feature of many vascular diseases is the contribution of reactive oxygen (ROS) and reactive nitrogen (RNS) species to vascular injury. Primary sources of ROS and RNS in smooth muscle are several isoforms of NADPH oxidase (Nox) and the cytokine-regulated inducible nitric oxide (NO) synthase (iNOS). One important example of the interaction between NO and ROS is the reaction of NO with superoxide to yield peroxynitrite, which may contribute to the pathogenesis of hypertension. In this review, we discuss the literature that supports an alternate possibility: Nox-derived ROS modulate NO bioavailability by altering the expression of iNOS. We highlight data showing coexpression of iNOS and Nox in vascular smooth muscle demonstrating the functional consequences of iNOS and Nox during vascular injury. We describe the relevant literature demonstrating that the mitogen-activated protein kinases are important modulators of proinflammatory cytokine-dependent expression of iNOS. A central hypothesis discussed is that ROS-dependent regulation of the serine/threonine kinase protein kinase C delta is essential to understanding how Nox may regulate signaling pathways leading to iNOS expression. Overall, the integration of nonphagocytic NADPH oxidase with cytokine signaling in general and in vascular smooth muscle in particular is poorly understood and merits further investigation. (C) 2007 Elsevier Inc. All rights reserved.
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