Rho Kinases in Health and Disease: From Basic Science to Translational Research

Loirand, Gervaise

doi:10.1124/pr.115.010595

Cited by 151 publications

(132 citation statements)

References 212 publications

(223 reference statements)

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“…By keeping MYPT-1 inactive, ROCK triggers MLC phosphorylation, cytosolic Ca +2 level increase and as a result it's contraction. 13 AMPKs vascular effect is the opposite of this. In contrast to ROCKs effect, AMPK activation increases the activity of eNOS in arterial smooth muscle.…”

Section: Rho-kinase and Adenosine Monophosphate-activated Protein Kinmentioning

confidence: 95%

“…ROCK are the first and most important effectors of the RhoA. 13,14 There are two isoforms of ROCK, namely, ROCK1 and ROCK2.…”

Section: Rho-kinase Pathwaymentioning

confidence: 99%

“…In the vascular smooth muscle, the MLC is phosphorylated by the MLC kinase, (MLCK) which is activated by Ca +2 -calmoduline-dependent kinase, and dephosphorylated by the Ca +2 -independent MLC phosphatase (MLCP). 13,14 The MLC, which gets phosphorylated with the activation of the MLCK, mediates the increase of the cytosolic Ca +2 concentration and the vascular smooth muscle contraction occurs (Figure 2). 12 ROCK inhibits the production of NO from the endothelium cells.…”

Section: Rho-kinase Pathwaymentioning

confidence: 99%

“…The activation of RhoA/ROCK decreases the endotelial NO synthase (eNOS) expression by inhibiting the eNOS mRNA stability. 13 It was shown that the eNOS expression increases during the treatment of human umbilical vein endothelial cells channel via the incubation of ROCK inhibitor Y27632 (10 μmol/L). 17 Among the ROCK inhibitors, only the fasudil is approved for the clinical use in the cerebral vasospasm endication.…”

Section: Rho-kinase Pathwaymentioning

confidence: 99%

See 3 more Smart Citations

Contribution of Rho-kinase and Adenosine Monophosphate-Activated Protein Kinase Signaling Pathways to Endothelium-Derived Contracting Factors Responses

Balcilar

Özakça

Altan

2017

tjps

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Vascular tonus is controlled by endothelium-derived relaxing factor (EDRF), endothelium-derived hyperpolarizing factor (EDHF) and endotheliumderived contracting factor (EDCF) under physiological circumstances. In pathological conditions, impairment of endothelium-derived relaxation can be caused by both decrease in EDRF release and increase in EDCF release. The increase in EDCF is observed with diseases such as hypertension and diabetes. The contribution of Rho-kinase and activated protein kinase (AMPK), which have opposite effects, to the increased EDCF responses was investigated. Rho-kinases are the effectors of Rho which is one of the small guanosine triphosphate-binding proteins. They increase cytosolic Ca +2 concentration and cause vascular smooth muscle to contract, keeping myosin light chain (MLC) in phosphorylated state by affecting myosin phosphatase target subunit which dephosphorylates the MLC. The activities of Rho-kinases increase with the increase of EDCF function. AMPK is the energy sensor of the cell. It provides a vasculoprotective effect by causing endothelium-dependent and endothelium-independent relaxation in smooth muscle. In contrast to Rho-kinase pathway activity, AMPK pathway activity decreases with diseases in which the EDCF function increases. In cases such as diabetes and hypertension that endothelial function impairs toward vasocontraction, it is considered that evaluating Rho-kinase and AMPK pathways which mediate contraction and relaxation in vascular smooth muscle respectively, would provide clues on choosing therapeutic target for pathologies in which endothelial dysfunction is observed. ÖZFizyolojik koşullarda vasküler tonus endotel kaynaklı rahatlatıcı faktörü (EDRF), endotel kaynaklı hiperpolarizasyon faktörü (EDHF) ve endotel kaynaklı kasılma faktörü (EDCF) tarafından kontrol edilmektedir. Patolojik durumlarda endotel kaynaklı gevşemenin azalması, EDRF üretimindeki azalmaya bağlı olabileceği gibi EDCF düzeyinin artmasına da bağlı olabilmektedir. EDCF hipertansiyon, diyabet gibi hastalıklarda artmaktadır. Diyabet, hipertansiyon gibi patolojik koşullarda artan EDCF yanıtına birbirine ters etki yapan Rho-kinaz ve aktive protein kinaz (AMPK) yolaklarının katkısı olabileceği düşünülmektedir. Rho-kinazlar küçük guanozin trifosfat-bağlı proteinlerden biri olan Rho'nun efektörüdür. Rho-kinazlar hafif zincir miyozini (MLC) defosforile eden miyozin fosfataz hedef altbirimine etki ederek MLC'nin fosforile halde kalmasının sağlayarak sitozolik Ca +2 konsantrasyonu artırır ve vasküler düz kasın kasılmasına neden olurlar. Rho-kinazların aktivitesi EDCF yanıtlarının arttığı hipertansiyon, kalp yetmezliği ve diyabet gibi hastalıklarda artmaktadır. AMPK ise hücrenin enerji sensörü olarak düşünülmektedir. Vasküler düz kasta endotel bağımlı ve bağımsız gevşemeyi sağlayarak vasküloprotektif etki sağlamaktadır. AMPK'nin aktivitesi Rho-kinaz yolağının aktivitesinin tersine EDCF fonksiyonunun arttığı hipertansiyon ve diyabet gibi hastalıklarda azalmaktadır. Endotel fonksiyonunun vazokonstriksiyon y...

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Section: Rho-kinase and Adenosine Monophosphate-activated Protein Kinmentioning

confidence: 95%

“…ROCK are the first and most important effectors of the RhoA. 13,14 There are two isoforms of ROCK, namely, ROCK1 and ROCK2.…”

Section: Rho-kinase Pathwaymentioning

confidence: 99%

Section: Rho-kinase Pathwaymentioning

confidence: 99%

Section: Rho-kinase Pathwaymentioning

confidence: 99%

See 2 more Smart Citations

Contribution of Rho-kinase and Adenosine Monophosphate-Activated Protein Kinase Signaling Pathways to Endothelium-Derived Contracting Factors Responses

Balcilar

Özakça

Altan

2017

tjps

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show abstract

“…Mounting evidence has shown that ROCKs act as determinant molecular switches controlling several critical cellular functions, such as proliferation and apoptosis, cytoskeletal rearrangement, cell adhesion and migration, inflammation, and reactive oxygen species formation [8][9][10]. Fasudil, a potent and selective ROCK inhibitor, showed clinical effectiveness and safety in the treatments of cardiovascular and cerebrovascular diseases, such as aneurysmal subarachnoid hemorrhage and myocardial ischemia [11,12].…”

Section: Introductionmentioning

confidence: 99%

Fasudil Attenuates LPS-Induced Acute Lung Injury by Preventing Endothelial Dysfunction

Wang¹,

Xu²,

Zhao³

et al. 2017

Preprint

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Fasudil, a potent Rho kinase (ROCK) inhibitor, can ameliorate LPS-induced acute lung injury (ALI) in mice, but the mechanism remains obscure. In this study, a mice model of ALI was established by intra-tracheal instillation of LPS.Histological changes, cytokine levels, lung permeability, and endothelial apoptosis were determined to evaluate the effects of fasudil on lung injury. The cellular and molecular biological mechanisms were explored by culturing human pulmonary

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Silk Sericin is a Potent, Multifunctional Biomaterial for Endothelialization of Tissue‐Engineered Heart Valves

Song,

Wang,

et al. 2024

Adv Funct Materials

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Endothelialization is important for offering an anticoagulant surface, which is crucial for the construction of tissue‐engineered heart valves. Silk sericin is extensively investigated in the biomedical field due to its remarkable biological activities and diverse functional groups, favoring chemical modifications for the formation of versatile constructs. Herein, a sericin covalently modified valve (SCMV) is successfully fabricated by coupling maleylated silk sericin (MSS) with thiolated decellularized heart valve (DHV) through a Michael addition reaction. The results demonstrate that SCMV exhibits a smooth surface, higher hydrophilicity, and excellent resistance to platelets adhesion compared to DHV. Additionally, SCMV promotes endothelial cells (ECs) adhesion under both static and flow conditions and enhances their survival in a mouse subcutaneous implant model. The study also discovered that MSS‐stimulated ECs exhibit increased RhoA activation, expression of rho‐associated protein kinase 2 (ROCK2) and phosphorylated myosin light chain 2 (MLC2), actin polymerization, and cell adhesion; whereas actin organization and cell adhesion are significantly reduced by treatment with Y‐27632, a ROCK inhibitor. Furthermore, several integrin subunits, including α1, α2, α3, α5, α6, β1, β3, and β5, are involved in this regulatory process. Collectively, the findings highlight the potential application of silk sericin in promoting endothelialization of DHV while uncovering novel mechanisms underlying its regulatory effect on ECs adhesion.

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Rho Kinases in Health and Disease: From Basic Science to Translational Research

Cited by 151 publications

References 212 publications

Contribution of Rho-kinase and Adenosine Monophosphate-Activated Protein Kinase Signaling Pathways to Endothelium-Derived Contracting Factors Responses

Contribution of Rho-kinase and Adenosine Monophosphate-Activated Protein Kinase Signaling Pathways to Endothelium-Derived Contracting Factors Responses

Fasudil Attenuates LPS-Induced Acute Lung Injury by Preventing Endothelial Dysfunction

Silk Sericin is a Potent, Multifunctional Biomaterial for Endothelialization of Tissue‐Engineered Heart Valves

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