The function of Rho-dependent kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00276/full |
| _version_ | 1817969061936496640 |
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| author | Svenja eHartmann Svenja eHartmann Anne J. Ridley Susanne eLutz |
| author_facet | Svenja eHartmann Svenja eHartmann Anne J. Ridley Susanne eLutz |
| author_sort | Svenja eHartmann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T20:16:38Z |
| format | Article |
| id | doaj.art-afcfad26f67c4cbcb4f5264eff5dd52f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T20:16:38Z |
| publishDate | 2015-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-afcfad26f67c4cbcb4f5264eff5dd52f2022-12-22T02:31:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122015-11-01610.3389/fphar.2015.00276158579The function of Rho-dependent kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular diseaseSvenja eHartmann0Svenja eHartmann1Anne J. Ridley2Susanne eLutz3University Medical Center, GoettingenKing's College LondonKing's College LondonUniversity Medical Center, GoettingenRho-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.http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00276/fullFibrosisHeartHypertrophycardiovascular diseaserho-kinaseinhibitor |
| spellingShingle | Svenja eHartmann Svenja eHartmann Anne J. Ridley Susanne eLutz The function of Rho-dependent kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease Frontiers in Pharmacology Fibrosis Heart Hypertrophy cardiovascular disease rho-kinase inhibitor |
| title | The function of Rho-dependent kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease |
| title_full | The function of Rho-dependent kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease |
| title_fullStr | The function of Rho-dependent kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease |
| title_full_unstemmed | The function of Rho-dependent kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease |
| title_short | The function of Rho-dependent kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease |
| title_sort | function of rho dependent kinases rock1 and rock2 in the pathogenesis of cardiovascular disease |
| topic | Fibrosis Heart Hypertrophy cardiovascular disease rho-kinase inhibitor |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2015.00276/full |
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