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2015 ; 6
(ä): 276
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English Wikipedia
The Function of Rho-Associated Kinases ROCK1 and ROCK2 in the Pathogenesis of
Cardiovascular Disease
#MMPMID26635606
Hartmann S
; Ridley AJ
; Lutz S
Front Pharmacol
2015[]; 6
(ä): 276
PMID26635606
show ga
Rho-associated kinases ROCK1 and ROCK2 are serine/threonine kinases that are
downstream targets of the small GTPases RhoA, RhoB, and RhoC. ROCKs are involved
in diverse cellular activities including actin cytoskeleton organization, cell
adhesion and motility, proliferation and apoptosis, remodeling of the
extracellular matrix and smooth muscle cell contraction. The role of ROCK1 and
ROCK2 has long been considered to be similar; however, it is now clear that they
do not always have the same functions. Moreover, depending on their subcellular
localization, activation, and other environmental factors, ROCK signaling can
have different effects on cellular function. With respect to the heart, findings
in isoform-specific knockout mice argue for a role of ROCK1 and ROCK2 in the
pathogenesis of cardiac fibrosis and cardiac hypertrophy, respectively. Increased
ROCK activity could play a pivotal role in processes leading to cardiovascular
diseases such as hypertension, pulmonary hypertension, angina pectoris,
vasospastic angina, heart failure, and stroke, and thus ROCK activity is a
potential new biomarker for heart disease. Pharmacological ROCK inhibition
reduces the enhanced ROCK activity in patients, accompanied with a measurable
improvement in medical condition. In this review, we focus on recent findings
regarding ROCK signaling in the pathogenesis of cardiovascular disease, with a
special focus on differences between ROCK1 and ROCK2 function.