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Redox control of vascular smooth muscle cell function and plasticity

Laboratory Investigationvolume 98pages12541262 (2018) | Download Citation


Vascular smooth muscle cells (SMC) play a major role in vascular diseases, such as atherosclerosis and hypertension. It has long been established in vitro that contractile SMC can phenotypically switch to function as proliferative and/or migratory cells in response to stimulation by oxidative stress, growth factors, and inflammatory cytokines. Reactive oxygen species (ROS) are oxidative stressors implicated in driving vascular diseases, shifting cell bioenergetics, and increasing SMC proliferation, migration, and apoptosis. In this review, we summarize our current knowledge of how disruptions to redox balance can functionally change SMC and how this may influence vascular disease pathogenesis. Specifically, we focus on our current understanding of the role of vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) 1, 4, and 5 in SMC function. We also review the evidence implicating mitochondrial fission in SMC phenotypic transitions and mitochondrial fusion in maintenance of SMC homeostasis. Finally, we discuss the importance of the redox regulation of the soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway as a potential oxidative and therapeutic target for regulating SMC function.

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Financial support was provided by the National Institutes of Health Grants R01 HL 133864, R01 HL 128304, American Heart Association (AHA) Grant-in-Aid 16GRNT27250146 (ACS). This work was further supported by the Institute for Transfusion Medicine and the Hemophilia Center of Western Pennsylvania (ACS). We would like to acknowledge the contributions of Katherine C. Wood and Joseph C. Galley for their aid in critical analysis of the manuscript.

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  1. Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA

    • Brittany G. Durgin
    •  & Adam C. Straub
  2. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA

    • Adam C. Straub


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Correspondence to Adam C. Straub.

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