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(Cardiology Div., Emory
Masuko Ushio-Fukai (Cardiology Div., Emory University, USA)
Kathy K. Griendling (Cardiology Div., Emory University, USA)
Contact Person: Bernard Lassègue (email@example.com)
Many effects of angiotensin II (AngII) in vascular disease are ascribed to its potent stimulation of vascular smooth muscle cells (vsmc). Within seconds of AngII binding to the AT1 receptor, phospholipase Cß1 is activated by heterotrimeric G protein subunits q/11, 12 and ß. PLC is subsequently activated by a tyrosine kinase. Transient activation of PLCs is followed by sustained phospholipase D activation via G protein subunits 12, ß, calcium, protein kinase C and src. Concomitantly, stimulation of phospholipase A2 initiates arachidonic acid signalling. Internalization of the AT1 receptor/agonist complex into membrane domains such as caveolae where effectors are localized is required for sustained AngII signalling. AngII also activates members of kinase cascades such as JAK/TYK/STAT, src, ras, and MAPK. Recently, reactive oxygen species have emerged as crucial components of AngII-mediated signal transduction in vsmc. Both superoxide and hydrogen peroxide are produced intracellularly via activation of an NADH oxidase, and these molecules serve to mediate downstream signalling events such as activation of p38MAPK and gene transcription. Thus, AngII activates a remarkable spectrum of signalling pathways, and the integration of these diverse signals directs and modulates the physiological and pathophysiological effects of this hormone on vsmc.
Presentation Number: SAlassegue0362
Keywords: angiotensin II, vascular smooth muscle, signalling, phospholipases, G proteins, superoxide.
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