TY - JOUR
T1 - The function of rho-associated kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease
AU - Hartmann, Svenja
AU - Ridley, Anne J.
AU - Lutz, Susanne
PY - 2015/11/20
Y1 - 2015/11/20
N2 - 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.
AB - 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.
KW - Cardiovascular disease
KW - Fibrosis
KW - Heart
KW - Hypertrophy
KW - Inhibitor
KW - Rho-kinase
KW - ROCK
KW - ROCK signaling
UR - http://www.scopus.com/inward/record.url?scp=84949769682&partnerID=8YFLogxK
U2 - 10.3389/fphar.2015.00276
DO - 10.3389/fphar.2015.00276
M3 - Article
AN - SCOPUS:84949769682
SN - 1663-9812
VL - 6
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
IS - NOV
M1 - 276
ER -
