Novel aspects of angiotensin II signalling
in vascular
smooth muscle
Bernard Lassègue
(Cardiology Div., Emory
University,
USA)
Masuko
Ushio-Fukai (Cardiology Div., Emory
University, USA)
Kathy K.
Griendling (Cardiology Div., Emory
University, USA)
Contact Person: Bernard Lassègue (medbpl@emory.edu)
Abstract
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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