PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32694763-0 2020 Author Correction: Simvastatin reduces the carcinogenic effect of 3-methylcholanthrene in renal epithelial cells through histone deacetylase 1 inhibition and RhoA reactivation. Simvastatin 19-30 ras homolog family member A Homo sapiens 158-162 35601076-0 2022 Simvastatin alleviates epithelial-mesenchymal transition and oxidative stress of high glucose-induced lens epithelial cells in vitro by inhibiting RhoA/ROCK signaling. Simvastatin 0-11 ras homolog family member A Homo sapiens 147-151 33597925-0 2020 Simvastatin and ROCK Inhibitor Y-27632 Inhibit Myofibroblast Differentiation of Graves" Ophthalmopathy-Derived Orbital Fibroblasts via RhoA-Mediated ERK and p38 Signaling Pathways. Simvastatin 0-11 ras homolog family member A Homo sapiens 135-139 33597925-4 2020 The inhibitory effect of simvastatin on TGF-beta-induced RhoA, ROCK1, and alpha-SMA expression could be reversed by geranylgeranyl pyrophosphate, an intermediate in the biosynthesis of cholesterol. Simvastatin 25-36 ras homolog family member A Homo sapiens 57-61 33597925-5 2020 This suggested that the mechanism of simvastatin-mediated antifibrotic effects may involve RhoA/ROCK signaling. Simvastatin 37-48 ras homolog family member A Homo sapiens 91-95 33597925-8 2020 These results suggested that simvastatin inhibits TGF-beta-induced myofibroblast differentiation via suppression of the RhoA/ROCK/ERK and p38 MAPK signaling pathways. Simvastatin 29-40 ras homolog family member A Homo sapiens 120-124 33897882-10 2021 Importantly, targeting MYBL2, or treatment with either the YAP/TAZ inhibitor Verteporfin or the RhoA inhibitor Simvastatin, reversed the resistance to ADT and blocked bone metastasis in CRPC cells. Simvastatin 111-122 ras homolog family member A Homo sapiens 96-100 30872677-6 2019 Simvastatin abolished the detrimental effects of 3MC by reducing HDAC1 expression, with resulting RhoA upregulation, and reactivating RhoA in vitro and in vivo. Simvastatin 0-11 ras homolog family member A Homo sapiens 134-138 32210573-9 2020 Further investigation revealed that simvastatin mainly acted through by inhibiting the activity of RhoA to inhibit YAP and beta-catenin, and the geranylgeranyl pyrophosphate pathway mediated this regulation. Simvastatin 36-47 ras homolog family member A Homo sapiens 99-103 30872677-0 2019 Simvastatin reduces the carcinogenic effect of 3-methylcholanthrene in renal epithelial cells through histone deacetylase 1 inhibition and RhoA reactivation. Simvastatin 0-11 ras homolog family member A Homo sapiens 139-143 30872677-6 2019 Simvastatin abolished the detrimental effects of 3MC by reducing HDAC1 expression, with resulting RhoA upregulation, and reactivating RhoA in vitro and in vivo. Simvastatin 0-11 ras homolog family member A Homo sapiens 98-102 30872677-9 2019 Collectively, these results demonstrate that simvastatin restores RhoA function through HDAC1 inhibition; therefore, simvastatin might serve as adjunct therapy for RCC induced by 3MC. Simvastatin 45-56 ras homolog family member A Homo sapiens 66-70 30872677-9 2019 Collectively, these results demonstrate that simvastatin restores RhoA function through HDAC1 inhibition; therefore, simvastatin might serve as adjunct therapy for RCC induced by 3MC. Simvastatin 117-128 ras homolog family member A Homo sapiens 66-70 29236027-6 2017 Immunoblotting analysis illustrated that simvastatin diminished the activation of RhoA and Rac1 protein, and this effect was prevented by pre-treatment with MEV and GGpp. Simvastatin 41-52 ras homolog family member A Homo sapiens 82-86 29319354-12 2018 The MCTP + simvastatin + mevalonate group, MCTP + simvastatin+ FPP group, and MCTP + simvastatin + FPP + GGPP group showed increased mRNA levels of RhoA and ROCK1, as well as increased protein levels of RhoA, compared to the MCTP + simvastatin group. Simvastatin 50-61 ras homolog family member A Homo sapiens 148-152 29319354-12 2018 The MCTP + simvastatin + mevalonate group, MCTP + simvastatin+ FPP group, and MCTP + simvastatin + FPP + GGPP group showed increased mRNA levels of RhoA and ROCK1, as well as increased protein levels of RhoA, compared to the MCTP + simvastatin group. Simvastatin 50-61 ras homolog family member A Homo sapiens 148-152 29319354-14 2018 The effects of simvastatin were mediated by inhibition of RhoA/ROCK1. Simvastatin 15-26 ras homolog family member A Homo sapiens 58-62 29319354-15 2018 Simvastatin decreased RhoA/ROCK1 overexpression by inhibition of mevalonate, FPP, and GGPP synthesis. Simvastatin 0-11 ras homolog family member A Homo sapiens 22-26 29604489-9 2018 Simvastatin appears to inhibit neutrophil adhesion by interfering in TNF-induced cytoskeletal rearrangements, in association with the inhibition of Rho A activity, NFkappaB translocation and, consequently, beta2-integrin activity. Simvastatin 0-11 ras homolog family member A Homo sapiens 148-153 29319354-0 2018 Inhibition of the RhoA/Rho-associated, coiled-coil-containing protein kinase-1 pathway is involved in the therapeutic effects of simvastatin on pulmonary arterial hypertension. Simvastatin 129-140 ras homolog family member A Homo sapiens 18-22 29319354-2 2018 This study aimed to investigate the role of RhoA/ROCK1 regulation in the therapeutic effects of simvastatin on PAH. Simvastatin 96-107 ras homolog family member A Homo sapiens 44-48 29319354-12 2018 The MCTP + simvastatin + mevalonate group, MCTP + simvastatin+ FPP group, and MCTP + simvastatin + FPP + GGPP group showed increased mRNA levels of RhoA and ROCK1, as well as increased protein levels of RhoA, compared to the MCTP + simvastatin group. Simvastatin 11-22 ras homolog family member A Homo sapiens 148-152 29319354-12 2018 The MCTP + simvastatin + mevalonate group, MCTP + simvastatin+ FPP group, and MCTP + simvastatin + FPP + GGPP group showed increased mRNA levels of RhoA and ROCK1, as well as increased protein levels of RhoA, compared to the MCTP + simvastatin group. Simvastatin 11-22 ras homolog family member A Homo sapiens 203-207 29319354-12 2018 The MCTP + simvastatin + mevalonate group, MCTP + simvastatin+ FPP group, and MCTP + simvastatin + FPP + GGPP group showed increased mRNA levels of RhoA and ROCK1, as well as increased protein levels of RhoA, compared to the MCTP + simvastatin group. Simvastatin 50-61 ras homolog family member A Homo sapiens 148-152 29236027-11 2017 Taken together, these results suggest that simvastatin induced ATC proliferation inhibition through the deactivation of RhoA/Rac1 protein and overexpression of p21cip and p27kip, and migration inhibition through the abrogation of Cyr61 protein expression. Simvastatin 43-54 ras homolog family member A Homo sapiens 120-124 29039527-4 2017 In the present study, we hypothesized that simvastatin, likely through the inhibition of farnesylation and geranylgeranylation of Rac1, Cd42 and RhoA, induces a destruction/restructuration of the cytoskeleton that decreases mechanical strain transfer to the nuclei, inducing the loss of transmission of regulatory signals from the cytoskeleton to the nucleoskeleton. Simvastatin 43-54 ras homolog family member A Homo sapiens 145-149 26451103-4 2015 We thus hypothesized that RhoA signaling is involved in simvastatin-induced osteogenesis in bone marrow mesenchymal stem cells. Simvastatin 56-67 ras homolog family member A Homo sapiens 26-30 28344327-5 2017 We confirmed that simvastatin caused the translocation of the small Rho GTPases RhoA, Cdc42, and Rac1/2/3 from cell membranes to the cytosol in U251 (glioblastoma), A549 (lung adenocarcinoma) and MDA-MB-231(breast cancer). Simvastatin 18-29 ras homolog family member A Homo sapiens 80-84 27180285-6 2016 We report that simvastatin significantly inhibits RhoA and Rab4, and Rab6 isoprenylation at doses as low as 50nM in vitro. Simvastatin 15-26 ras homolog family member A Homo sapiens 50-54 26451103-5 2015 We found that although treatment with simvastatin shifts localization of RhoA protein from the membrane to the cytosol, the treatment still activates RhoA dose-dependently because it reduces the association with RhoGDIalpha. Simvastatin 38-49 ras homolog family member A Homo sapiens 73-77 26451103-5 2015 We found that although treatment with simvastatin shifts localization of RhoA protein from the membrane to the cytosol, the treatment still activates RhoA dose-dependently because it reduces the association with RhoGDIalpha. Simvastatin 38-49 ras homolog family member A Homo sapiens 150-154 24535918-8 2014 Considering the essential role of RhoA activation in cell migration, we evaluated the potential use of simvastatin, a RhoA inhibitor, as a therapeutic intervention in vivo using matrigel plug formation assays. Simvastatin 103-114 ras homolog family member A Homo sapiens 118-122 26207907-0 2015 Simvastatin Increases Fibulin-2 Expression in Human Coronary Artery Smooth Muscle Cells via RhoA/Rho-Kinase Signaling Pathway Inhibition. Simvastatin 0-11 ras homolog family member A Homo sapiens 92-96 26207907-11 2015 Simvastatin increased mRNA levels and protein expression of the ECM protein fibulin-2 through a RhoA and Rho-Kinase-mediated pathway. Simvastatin 0-11 ras homolog family member A Homo sapiens 96-100 24535918-9 2014 Our results provide a molecular basis for the therapeutic application of simvastatin to reduce RhoA/PTEN activation, restore cytosolic levels of phosphorylated p21/p27, and induce angiogenic processes. Simvastatin 73-84 ras homolog family member A Homo sapiens 95-99 24582560-11 2014 Moreover, we observed that simvastatin decreased CCL17-induced activation of RhoA in colon cancer cells. Simvastatin 27-38 ras homolog family member A Homo sapiens 77-81 25023790-11 2014 Simvastatin suppressed cardiac RhoA mobilization and triggered Akt/eNOS signaling. Simvastatin 0-11 ras homolog family member A Homo sapiens 31-35 24582560-12 2014 Administration of mevalonate and GGPP reversed the inhibitory effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells. Simvastatin 72-83 ras homolog family member A Homo sapiens 102-106 23424259-0 2013 A transcriptomics-informed genetic association study identifies RHOA in simvastatin-induced low-density lipoprotein cholesterol lowering. Simvastatin 72-83 ras homolog family member A Homo sapiens 64-68 23559002-0 2013 Deciphering the signaling networks underlying simvastatin-induced apoptosis in human cancer cells: evidence for non-canonical activation of RhoA and Rac1 GTPases. Simvastatin 46-57 ras homolog family member A Homo sapiens 140-144 23559002-4 2013 Indeed, simvastatin treatment led to increased levels of unprenylated Ras homolog gene family, member A (RhoA), Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42). Simvastatin 8-19 ras homolog family member A Homo sapiens 105-109 23559002-5 2013 Intriguingly, instead of inhibiting the functions of Rho GTPases as was expected with loss of prenylation, simvastatin caused a paradoxical increase in the GTP-bound forms of RhoA, Rac1 and Cdc42. Simvastatin 107-118 ras homolog family member A Homo sapiens 175-179 23559002-7 2013 We also show that the unprenylated RhoA- and Rac1-GTP retained at least part of their functional activities, as evidenced by the increase in intracellular superoxide production and JNK activation in response to simvastatin. Simvastatin 211-222 ras homolog family member A Homo sapiens 35-39 24471776-13 2014 A RhoA activation assay showed that preincubation with simvastatin significantly blocked TGF-beta1-induced RhoA activation. Simvastatin 55-66 ras homolog family member A Homo sapiens 2-6 24471776-13 2014 A RhoA activation assay showed that preincubation with simvastatin significantly blocked TGF-beta1-induced RhoA activation. Simvastatin 55-66 ras homolog family member A Homo sapiens 107-111 22451024-0 2013 Inhibitory effects of simvastatin on migration and invasion of rheumatoid fibroblast-like synoviocytes by preventing geranylgeranylation of RhoA. Simvastatin 22-33 ras homolog family member A Homo sapiens 140-144 22451024-6 2013 We also found that simvastatin suppressed in vitro invasion, adhesion, MMP-2 activity, cytoskeletal reorganization and RhoA activation. Simvastatin 19-30 ras homolog family member A Homo sapiens 119-123 22451024-7 2013 Furthermore, mevalonate or GGPP treatment reversed the inhibitory effect of simvastatin not only on migration and invasion in vitro but also on RhoA activation, and inhibition of RhoA by specific siRNA transfection reduced migration, adhesion and invasion of RA FLS. Simvastatin 76-87 ras homolog family member A Homo sapiens 144-148 22451024-7 2013 Furthermore, mevalonate or GGPP treatment reversed the inhibitory effect of simvastatin not only on migration and invasion in vitro but also on RhoA activation, and inhibition of RhoA by specific siRNA transfection reduced migration, adhesion and invasion of RA FLS. Simvastatin 76-87 ras homolog family member A Homo sapiens 179-183 22451024-8 2013 This study shows that simvastatin reduces RA FLS migration and invasion through the prevention of protein geranylgeranylation and RhoA activation. Simvastatin 22-33 ras homolog family member A Homo sapiens 130-134 22127053-5 2012 SPC treatment caused RhoA activation via a simvastatin-sensitive mechanism. Simvastatin 43-54 ras homolog family member A Homo sapiens 21-25 22127053-8 2012 These results suggest that simvastatin inhibits SPC-induced differentiation of hASCs into smooth muscle cells by attenuating the RhoA/Rho kinase-dependent activation of autocrine TGF-beta1/Smad2 signaling pathway. Simvastatin 27-38 ras homolog family member A Homo sapiens 129-133 20463291-9 2011 Moreover, simvastatin and GGTI-286 both prevented TGFbeta1-induced membrane association of RhoA, a downstream target of GGT1. Simvastatin 10-21 ras homolog family member A Homo sapiens 91-95 20473500-0 2011 HMG-CoA reductase inhibitor simvastatin suppresses Toll-like receptor 2 ligand-induced activation of nuclear factor kappa B by preventing RhoA activation in monocytes from rheumatoid arthritis patients. Simvastatin 28-39 ras homolog family member A Homo sapiens 138-142 20473500-1 2011 To investigate whether anti-inflammatory effects of HMG-CoA reductase inhibitor simvastatin (SMV) in rheumatoid arthritis (RA) is mediated by Toll-like receptor-2 (TLR-2) signal via inhibiting activation of RhoA, a small Rho GTPase that plays an important role in inflammatory responses. Simvastatin 80-91 ras homolog family member A Homo sapiens 207-211 21844074-4 2011 During allograft preservation, donor simvastatin treatment inhibited microvascular endothelial cell and pericyte RhoA/Rho-associated protein kinase activation and endothelial cell-endothelial cell gap formation; decreased intragraft mRNA levels of hypoxia-inducible factor-1alpha, inducible nitric oxide synthase, and endothelin-1; and increased heme oxygenase-1. Simvastatin 37-48 ras homolog family member A Homo sapiens 113-117 21844074-6 2011 The beneficial effects of simvastatin on vascular stability and the no-reflow phenomenon were abolished by concomitant nitric oxide synthase inhibition with N-nitro-l-arginine methyl ester and RhoA activation by geranylgeranyl pyrophosphate supplementation, respectively. Simvastatin 26-37 ras homolog family member A Homo sapiens 193-197 20463291-10 2011 Our findings suggest that simvastatin and GGTI-286 inhibit synthesis and secretion of extracellular matrix proteins by human airway smooth muscle cells by suppressing GGT1-mediated posttranslational modification of signaling molecules such as RhoA. Simvastatin 26-37 ras homolog family member A Homo sapiens 243-247 23166513-6 2012 Furthermore, inter-individual variation in statin-induced RHOA mRNA expression measured in vitro in CAP LCLs was correlated with the changes in plasma total cholesterol, LDL-cholesterol, and APOB induced by simvastatin treatment (40 mg/d for 6 wk) of the individuals from whom these cell lines were derived. Simvastatin 207-218 ras homolog family member A Homo sapiens 58-62 20473500-1 2011 To investigate whether anti-inflammatory effects of HMG-CoA reductase inhibitor simvastatin (SMV) in rheumatoid arthritis (RA) is mediated by Toll-like receptor-2 (TLR-2) signal via inhibiting activation of RhoA, a small Rho GTPase that plays an important role in inflammatory responses. Simvastatin 93-96 ras homolog family member A Homo sapiens 207-211 20473500-8 2011 SMV mitigated PG-induced increase in RhoA activity and NF-kappaB activation as well as secretion of TNFalpha and IL-1beta. Simvastatin 0-3 ras homolog family member A Homo sapiens 37-41 21052011-0 2011 Simvastatin reduces lipoprotein-associated phospholipase A2 in lipopolysaccharide-stimulated human monocyte-derived macrophages through inhibition of the mevalonate-geranylgeranyl pyrophosphate-RhoA-p38 mitogen-activated protein kinase pathway. Simvastatin 0-11 ras homolog family member A Homo sapiens 194-198 21052011-7 2011 In addition, treatment with simvastatin blocked LPS-induced activation of RhoA, which could be abolished by treatment with GGPP. Simvastatin 28-39 ras homolog family member A Homo sapiens 74-78 21052011-10 2011 Together, these results suggest that simvastatin reduces Lp-PLA(2) expression and secreted activity in LPS-stimulated human monocyte-derived macrophages through the inhibition of the mevalonate-GGPP-RhoA-p38 MAPK pathway. Simvastatin 37-48 ras homolog family member A Homo sapiens 199-203 20378830-6 2010 The decrease in the IAS tone by simvastatin was associated with the decrease in the prenylation of RhoA, as well as RhoA/ROCK in the membrane fractions of the IAS, in the basal state. Simvastatin 32-43 ras homolog family member A Homo sapiens 99-103 20378830-6 2010 The decrease in the IAS tone by simvastatin was associated with the decrease in the prenylation of RhoA, as well as RhoA/ROCK in the membrane fractions of the IAS, in the basal state. Simvastatin 32-43 ras homolog family member A Homo sapiens 116-120 20378830-8 2010 Relaxation of the IAS smooth muscle via HMGCRI simvastatin is mediated via the downstream decrease in the levels of RhoA prenylation and ROCK activity. Simvastatin 47-58 ras homolog family member A Homo sapiens 116-120 19001041-7 2009 RhoA activity decreased after 4 days simvastatin (P < 0.05); however, activity was no different from Control after 12 days. Simvastatin 37-48 ras homolog family member A Homo sapiens 0-4 19786891-8 2010 Immunofluorescence staining revealed that simvastatin (1 micromol/L) inhibited translocation of Rho A from the cytoplasm to membrane and disorganized actin fibers in PASMCs from patients with IPAH. Simvastatin 42-53 ras homolog family member A Homo sapiens 96-101 19001041-8 2009 Simvastatin down-regulated PI3k/Akt signalling, independently of RhoA, and up-regulated FOXO transcription factors and downstream gene targets known to be implicated in proteasomal- and lysosomal-mediated muscle proteolysis, carbohydrate oxidation, oxidative stress and inflammation in an in vivo model of statin-induced myopathy. Simvastatin 0-11 ras homolog family member A Homo sapiens 65-69 18981156-11 2008 In conclusion, simvastatin induces endothelial SR-BI expression through a RhoA- and peroxisome proliferator-activated receptor-alpha-dependent mechanism, thereby enhancing the HDL-induced activation of NOS and the inhibition of adhesion molecule expression. Simvastatin 15-26 ras homolog family member A Homo sapiens 74-78 18625202-6 2008 GGPP-dependent plasma membrane localization of the small GTPase RhoA that is required for RhoA-mediated oncogenic signaling is completely inhibited by simvastatin. Simvastatin 151-162 ras homolog family member A Homo sapiens 64-68 18658277-9 2008 Together, these data suggest EC barrier protection by simvastatin is due to dual inhibitory effects on RhoA and Rac1 as well as the attenuation of superoxide generation by EC NADPH oxidase and contribute to the molecular mechanistic understanding of the modulation of EC barrier properties by simvastatin. Simvastatin 54-65 ras homolog family member A Homo sapiens 103-107 18625202-6 2008 GGPP-dependent plasma membrane localization of the small GTPase RhoA that is required for RhoA-mediated oncogenic signaling is completely inhibited by simvastatin. Simvastatin 151-162 ras homolog family member A Homo sapiens 90-94 17217948-15 2007 Simvastatin and Y27632 reduced active RhoA-induced COL1A2 promoter activity. Simvastatin 0-11 ras homolog family member A Homo sapiens 38-42 18619957-9 2008 We further revealed that simvastatin suppression of RhoA activation mediated its inhibitory effect on angiotensin II-triggered MMP2 release. Simvastatin 25-36 ras homolog family member A Homo sapiens 52-56 18619957-10 2008 Similarly, simvastatin suppressed endothelin-1-induced MMP2 release through RhoA/ROCK pathway. Simvastatin 11-22 ras homolog family member A Homo sapiens 76-80 17452038-8 2008 CTGF upregulation by non-uniform shear stress was RhoA-dependent, because it was almost completely inhibited in cells transfected with dominant negative RhoA-N19, and when cells were treated with 1 micromol/L simvastatin during flow. Simvastatin 209-220 ras homolog family member A Homo sapiens 50-54 18463201-6 2008 The effects of simvastatin were due to the inhibition of the small G-protein RhoA and of its effector Rho kinase. Simvastatin 15-26 ras homolog family member A Homo sapiens 77-81 18356691-10 2008 CONCLUSIONS: Simvastatin stimulates VEGF expression by RhoA downregulation and HIF-1alpha upregulation in endothelial cells. Simvastatin 13-24 ras homolog family member A Homo sapiens 55-59 18199714-8 2008 Furthermore, lovastatin and simvastatin suppressed RhoA activation and c-JUN expression, but not cyclooxygenase-2 expression. Simvastatin 28-39 ras homolog family member A Homo sapiens 51-55 16740276-0 2006 Simvastatin potentiates tumor necrosis factor alpha-mediated apoptosis of human vascular endothelial cells via the inhibition of the geranylgeranylation of RhoA. Simvastatin 0-11 ras homolog family member A Homo sapiens 156-160 16858009-0 2006 Role of RhoA inactivation in reduced cell proliferation of human airway smooth muscle by simvastatin. Simvastatin 89-100 ras homolog family member A Homo sapiens 8-12 16858009-7 2006 The antiproliferative effects of simvastatin were mimicked by GGTI-286, a geranylgeranyltransferase-I inhibitor, C3 exoenzyme, an inhibitor of Rho, and Y-27632, an inhibitor of Rho-kinase, a target protein of RhoA. Simvastatin 33-44 ras homolog family member A Homo sapiens 209-213 16858009-8 2006 Western blot analysis showed that the level of membrane localization of RhoA (active Rho) was markedly increased by FBS, and that the level of active RhoA increased by FBS was reduced by simvastatin. Simvastatin 187-198 ras homolog family member A Homo sapiens 72-76 16858009-8 2006 Western blot analysis showed that the level of membrane localization of RhoA (active Rho) was markedly increased by FBS, and that the level of active RhoA increased by FBS was reduced by simvastatin. Simvastatin 187-198 ras homolog family member A Homo sapiens 150-154 16858009-9 2006 Moreover, the inhibitory effect of simvastatin on FBS-induced RhoA activation was also antagonized by geranylgeranylpyrophosphate, but not by farnesylpyrophosphate. Simvastatin 35-46 ras homolog family member A Homo sapiens 62-66 16858009-10 2006 Because these isoprenoids are required for prenylation of small G proteins RhoA and Ras, respectively, the present results demonstrate that an inhibition in airway smooth muscle cell proliferation by simvastatin is due to prevention of geranylgeranylation of RhoA, not farnesylation of Ras. Simvastatin 200-211 ras homolog family member A Homo sapiens 75-79 16858009-10 2006 Because these isoprenoids are required for prenylation of small G proteins RhoA and Ras, respectively, the present results demonstrate that an inhibition in airway smooth muscle cell proliferation by simvastatin is due to prevention of geranylgeranylation of RhoA, not farnesylation of Ras. Simvastatin 200-211 ras homolog family member A Homo sapiens 259-263 16774905-0 2006 HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced "inside-out" signaling to extracellular matrix by preventing RhoA activation. Simvastatin 28-39 ras homolog family member A Homo sapiens 124-128 16774905-8 2006 Our data also indicate that simvastatin, via mevalonate depletion, reverses VEGF-induced ECM accumulation by preventing RhoA activation. Simvastatin 28-39 ras homolog family member A Homo sapiens 120-124 17075836-0 2006 RhoA-mediated, tumor necrosis factor alpha-induced activation of NF-kappaB in rheumatoid synoviocytes: inhibitory effect of simvastatin. Simvastatin 124-135 ras homolog family member A Homo sapiens 0-4 17075836-8 2006 SMV prevented the increase in NF-kappaB activation and rise in IL-1beta and IL-6 levels induced by TNFalpha, whereas mevalonate and geranylgeranyl pyrophosphate reversed the inhibitory effects of SMV on activation of NF-kappaB and RhoA. Simvastatin 0-3 ras homolog family member A Homo sapiens 231-235 16740276-4 2006 Geranylgeraniol, which serves as a substrate for the geranylgeranylation of small GTP binding proteins such as RhoA, which is required for the function and membrane localization of Rho, reversed the effect of simvastatin on apoptosis. Simvastatin 209-220 ras homolog family member A Homo sapiens 111-115 16740276-7 2006 Adenoviral expression of a dominant-negative RhoA mimicked the effect of simvastatin on the expression of TNFalphaRI, while adenoviral expression of a dominant-activating RhoA mutant reversed the effect of simvastatin on the expression of TNFalphaRI. Simvastatin 73-84 ras homolog family member A Homo sapiens 45-49 16740276-7 2006 Adenoviral expression of a dominant-negative RhoA mimicked the effect of simvastatin on the expression of TNFalphaRI, while adenoviral expression of a dominant-activating RhoA mutant reversed the effect of simvastatin on the expression of TNFalphaRI. Simvastatin 206-217 ras homolog family member A Homo sapiens 171-175 16775505-14 2006 Simvastatin (10 micromol/L) and cerivastatin (10 micromol/L) significantly decreased thrombin-induced membrane translocation of Rho A. Simvastatin 0-11 ras homolog family member A Homo sapiens 128-133 12951326-6 2003 Interference with RhoA signaling by simvastatin, toxinB, C3 toxin, and Y27632 prevented up-regulation of CTGF. Simvastatin 36-47 ras homolog family member A Homo sapiens 18-22 17237547-8 2006 Adenoviral expression of a DN-RhoA mutant mimicked the effect of simvastatin on tube formation and the formation of honeycombs, whereas a dominant activating mutant of RhoA reversed the effect of simvastatin on tube formation. Simvastatin 65-76 ras homolog family member A Homo sapiens 30-34 17237547-8 2006 Adenoviral expression of a DN-RhoA mutant mimicked the effect of simvastatin on tube formation and the formation of honeycombs, whereas a dominant activating mutant of RhoA reversed the effect of simvastatin on tube formation. Simvastatin 196-207 ras homolog family member A Homo sapiens 168-172 17237547-9 2006 Finally, simvastatin interfered with the membrane localization of RhoA with a dose-dependence similar to that for the inhibition of tube formation. Simvastatin 9-20 ras homolog family member A Homo sapiens 66-70 17237547-11 2006 These data demonstrate that simvastatin interfered with angiogenesis via the inhibition of RhoA. Simvastatin 28-39 ras homolog family member A Homo sapiens 91-95 15728660-0 2005 Simvastatin inhibits MMP-9 secretion from human saphenous vein smooth muscle cells by inhibiting the RhoA/ROCK pathway and reducing MMP-9 mRNA levels. Simvastatin 0-11 ras homolog family member A Homo sapiens 101-105 15728660-11 2005 Together these data suggest that simvastatin reduces MMP-9 secretion from human SV-SMC by inhibiting the RhoA/ROCK pathway and decreasing MMP-9 mRNA levels independently of effects on signaling pathways required for MMP-9 gene expression. Simvastatin 33-44 ras homolog family member A Homo sapiens 105-109 15339992-8 2004 EC proliferation and cell cycle progression, examined by 5,6-carboxyfluorescein diacetate succinimidyl ester staining, demonstrated that anti-HLA-induced EC proliferation was efficiently prevented by the 3-hydroxy-3-methylglutaryl CoA reductase inhibitor simvastatin (0.1 micromol/L) through inhibition of RhoA geranylgeranylation. Simvastatin 255-266 ras homolog family member A Homo sapiens 306-310 15339992-9 2004 Taken together, these findings support the conclusion that RhoA is a key mediator of signaling pathways that lead to cytoskeletal reorganization and EC proliferation in response to alloantibodies that bind to HLA class I and demonstrate the specific and potent inhibitory effect of simvastatin on allostimulated EC growth. Simvastatin 282-293 ras homolog family member A Homo sapiens 59-63 14985071-0 2004 Simvastatin reduces human atrial myofibroblast proliferation independently of cholesterol lowering via inhibition of RhoA. Simvastatin 0-11 ras homolog family member A Homo sapiens 117-121 14985071-11 2004 Furthermore, we demonstrated that simvastatin inhibited RhoA function by preventing its association with the plasma membrane and hence, its interaction with downstream effectors required for cell proliferation. Simvastatin 34-45 ras homolog family member A Homo sapiens 56-60 14985071-12 2004 CONCLUSIONS: Simvastatin reduced proliferation of cultured human atrial myofibroblasts independently of cholesterol synthesis via a mechanism involving inhibition of RhoA geranylgeranylation. Simvastatin 13-24 ras homolog family member A Homo sapiens 166-170 12477733-10 2003 Indeed, the isoprenylation of Ras and RhoA protein appeared normal in HIDS and MA fibroblasts under normal conditions but showed increased sensitivity toward inhibition of HMGR by simvastatin. Simvastatin 180-191 ras homolog family member A Homo sapiens 38-42 11882313-0 2002 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, atorvastatin and simvastatin, induce apoptosis of vascular smooth muscle cells by downregulation of Bcl-2 expression and Rho A prenylation. Simvastatin 78-89 ras homolog family member A Homo sapiens 182-187 12142347-8 2002 The expression of a dominant-activating RhoA mutant reversed the effect of simvastatin on tube formation. Simvastatin 75-86 ras homolog family member A Homo sapiens 40-44 11956113-12 2002 Simvastatin prevented thrombin-induced Rho A activation but not p38 MAP kinase activation. Simvastatin 0-11 ras homolog family member A Homo sapiens 39-44 11104736-7 2000 This reduction in barrier dysfunction by simvastatin was both dose and time dependent and was accompanied by a reduction in the thrombin-induced formation of stress fibers and focal adhesions and membrane association of RhoA. Simvastatin 41-52 ras homolog family member A Homo sapiens 220-224 11487529-7 2001 Simvastatin reduced the binding of the small GTPase RhoA to cellular membranes. Simvastatin 0-11 ras homolog family member A Homo sapiens 52-56