Author(s): Paravicini TM, Touyz RM
Diseases such as hypertension, atherosclerosis and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC) growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many stimuli influence cellular changes, including mechanical forces, such as shear stress, and vasoactive agents, of which angiotensin II (Ang II) appears to be amongst the most important. Ang II mediates many of its pleiotropic vascular effects through NAD(P)H oxidase-derived reactive oxygen species (ROS). Mechanical forces, comprising both unidirectional laminar and oscillatory shear, are increasingly being recognized as important inducers of vascular NO and ROS generation. In general, laminar flow is associated with upregulation of eNOS and NO production and increased expression of antioxidants glutathione peroxidase and superoxide dismutase, thereby promoting a healthy vascular wall and protecting against oxidative vascular injury. On the other hand, oscillatory shear is linked to increased ROS production with consequent oxidative damage, as occurs in hypertension. ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca(2+) concentration, a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, low concentrations of intracellular ROS play an important role in normal redox signaling involved in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review describes some of the redox-sensitive signaling pathways that are involved in the functional and structural vascular changes associated with hypertension.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/16765337
Author(s): Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, et al.
Author(s): Lee MY, Griendling KK
Author(s): Touyz RM
Author(s): De Artinano AA, Gonzalez VL
Author(s): Török J
Author(s): Kunes J, Hojná S, Kadlecová M, Dobesová Z, Rauchová H, et al.
Author(s): Richards TR, Tobe SW2
Author(s): Calhoun DA, Glazer RD, Pettyjohn FS, Coenen PD, Zhao Y, et al.
Author(s): Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, et al.
Author(s): Kumar N, Calhoun DA, Dudenbostel T
Author(s): Fredholm BB
Author(s): Del Ry S, Cabiati M, Lionetti V, Aquaro GD, Martino A, et al.
Author(s): Müller CE, Jacobson KA
Author(s): Eltzschig HK
Author(s): Johansson SM, Yang JN, Lindgren E, Fredholm BB
Author(s): Grenz A, Bauerle JD, Dalton JH, Ridyard D, Badulak A, et al.
Author(s): Sun D, Samuelson LC, Yang T, Huang Y, Paliege A, et al.
Author(s): Rosenberger P, Schwab JM, Mirakaj V, Masekowsky E, Mager A, et al.
Author(s): Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, et al.
Author(s): Lazarus M, Shen HY, Cherasse Y, Qu WM, Huang ZL, et al.
Author(s): Liu XL, Zhou R, Pan QQ, Jia XL, Gao WN, et al.
Author(s): Haskó G, Linden J, Cronstein B, Pacher P
Author(s): Eltzschig HK, Eckle T
Author(s): Antonioli L, Fornai M, Colucci R, Ghisu N, Tuccori M, et al.
Author(s): Zhou Y, Schneider DJ, Blackburn MR
Author(s): Haskó G, Cronstein BN
Author(s): Caruso M, Alamo A, Crisafulli E, Raciti C, Fisichella A, et al.
Author(s): Karmouty-Quintana H, Xia Y, Blackburn MR
Author(s): Fredholm BB, Arslan G, Halldner L, Kull B, Schulte G, et al.