Mechanosensitive production of reactive oxygen species in endothelial and smooth muscle cells: role in microvascular remodeling?
Changes in the hemodynamic environment (e.g., hypertension, increased blood flow/shear stress) are known to lead to vascular remodeling; however, the underlying mechanisms by which hemodynamic forces control gene expression in vascular cells are not yet completely understood. This review considers how mechanosensitive generation of reactive oxygen species (ROS) by NAD(P)H oxidases and other sources interacts with downstream signaling systems [including activation of nuclear factor kappa B (NF-kappaB) and AP-1] that modulate the phenotype of endothelial and smooth muscle cells, leading to vascular remodeling. We propose a model for an interaction between direct mechanosensitive ROS signaling and pathways activated by pressure-induced upregulation of prooxidant paracrine signaling mechanisms [local renin-angiotensin system, TNF-alpha- converting enzyme (TACE)/tumor necrosis factor alpha (TNF-alpha) system, and endothelin signaling].
Ungvari
Zoltan
Z
Department of Physiology, New York Medical College, Valhalla, 10595, USA. zoltan_ungvari@nymc.edu
Wolin
Michael S
MS
Csiszar
Anna
A
D051722:ADAM Proteins / Q000502:physiology; D000072198:ADAM17 Protein; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001794:Blood Pressure; D016232:Endothelins / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005544:Forecasting; D006973:Hypertension / Q000209:etiology; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D019899:Paracrine Communication / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation
D000975:Antioxidants; D016232:Endothelins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D019255:NADPH Oxidases; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat