Oxidation-sensitive transcription factors and molecular mechanisms in the arterial wall.
Adaptation to various forms of cellular stress involves signal transduction into the cytoplasm and subsequently into the cellular nucleus, and ultimately alteration of gene regulation and expression. Increased oxidative stress, which is associated with increased production of reactive oxygen species and other radical species, plays a pivotal role in vascular dysfunction and contributes substantially to the structural and functional changes leading to vascular disease progression. Activation of oxidation-sensitive transcription factors and molecular mechanisms can be triggered in the systemic, tissue, cellular, and molecular environments, thereby affecting a multitude of pathophysiological events involved in the pathogenesis of atherosclerosis and other vascular diseases. Radicals per se also participate in the pathophysiological vascular response to shear stress and injury. Among the oxidation-sensitive transcription factors, important roles have been ascribed to nuclear factor-kappaB, c-Myc, and the peroxisome proliferator-activated receptor family. Regulation of nuclear events has also been recently proposed to involve corepressor and coactivator molecules. Identification of the genes that are involved in these processes has been facilitated by recent development of microarray chip techniques, which allow simultaneous evaluation of differential gene expression. As many of the transcription factors or their interactions are redox-regulated, antioxidant intervention may affect their bioactivity.
De Nigris
F
F
Department of Medicine, University of Naples, Italy.
Lerman
L O
LO
Condorelli
M
M
Lerman
A
A
Napoli
C
C
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D005609:Free Radicals; D016328:NF-kappa B; D014157:Transcription Factors; D010100:Oxygen