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https://www.readbyqxmd.com/read/29189096/regulation-and-functions-of-rhou-and-rhov
#1
Richard G Hodge, Anne J Ridley
Rho GTPases play central roles in a wide variety of cellular processes, including cytoskeletal dynamics, cell adhesion and cell polarity. RhoU and RhoV are Rho GTPases that have some atypical properties compared with classical Rho family members, such as the presence of N- and C-terminal extension regions, unusual GDP/GTP cycling and post-translational modification by palmitoylation but not prenylation. Their activity and localization is regulated by the N-terminal and C-terminal regions, and so far no GEFs or GAPs have been identified for them...
November 30, 2017: Small GTPases
https://www.readbyqxmd.com/read/29136112/local-production-of-tenascin-c-acts-as-a-trigger-for-monocyte-macrophage-recruitment-that-provokes-cardiac-dysfunction
#2
Dounia Abbadi, Fanny Laroumanie, Mathilde Bizou, Joffrey Pozzo, Danièle Daviaud, Christine Delage, Denis Calise, Fréderique Gaits-Iacovoni, Marianne Dutaur, Florence Tortosa, Edith Renaud-Gabardos, Victorine Douin-Echinard, Anne-Catherine Prats, Jerome Roncalli, Angelo Parini, Nathalie Pizzinat
Aims: Tenascin-C (TNC) is an endogenous danger signal molecule strongly associated with inflammatory diseases and with poor outcome in patients with cardiomyopathies. Its function within pathological cardiac tissue during pressure overload remains poorly understood. Methods and results: We showed that TNC accumulates after 1 week of transverse aortic constriction (TAC) in the heart of 12-week-old male mice. By cross bone marrow transplantation experiments, we determined that TNC deposition relied on cardiac cells and not on haematopoietic cells...
November 10, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29066090/genetic-variants-associated-with-susceptibility-to-idiopathic-pulmonary-fibrosis-in-people-of-european-ancestry-a-genome-wide-association-study
#3
Richard J Allen, Joanne Porte, Rebecca Braybrooke, Carlos Flores, Tasha E Fingerlin, Justin M Oldham, Beatriz Guillen-Guio, Shwu-Fan Ma, Tsukasa Okamoto, Alison E John, Ma'en Obeidat, Ivana V Yang, Amanda Henry, Richard B Hubbard, Vidya Navaratnam, Gauri Saini, Norma Thompson, Helen L Booth, Simon P Hart, Mike R Hill, Nik Hirani, Toby M Maher, Robin J McAnulty, Ann B Millar, Philip L Molyneaux, Helen Parfrey, Doris M Rassl, Moira K B Whyte, William A Fahy, Richard P Marshall, Eunice Oballa, Yohan Bossé, David C Nickle, Don D Sin, Wim Timens, Nick Shrine, Ian Sayers, Ian P Hall, Imre Noth, David A Schwartz, Martin D Tobin, Louise V Wain, R Gisli Jenkins
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with high mortality, uncertain cause, and few treatment options. Studies have identified a significant genetic risk associated with the development of IPF; however, mechanisms by which genetic risk factors promote IPF remain unclear. We aimed to identify genetic variants associated with IPF susceptibility and provide mechanistic insight using gene and protein expression analyses. METHODS: We used a two-stage approach: a genome-wide association study in patients with IPF of European ancestry recruited from nine different centres in the UK and controls selected from UK Biobank (stage 1) matched for age, sex, and smoking status; and a follow-up of associated genetic variants in independent datasets of patients with IPF and controls from two independent US samples from the Chicago consortium and the Colorado consortium (stage 2)...
November 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29061365/rho-specific-guanine-nucleotide-exchange-factors-rho-gefs-inhibition-affects-macrophage-phenotype-and-disrupts-golgi-complex
#4
Wei Chen, Yue Zhao, Xian C Li, Jacek Z Kubiak, Rafik M Ghobrial, Malgorzata Kloc
Macrophages play crucial role in tissue homeostasis and the innate and adaptive immune response. Depending on the state of activation macrophages acquire distinct phenotypes that depend on actin, which is regulated by small GTPase RhoA. The naive M0 macrophages are slightly elongated, pro-inflammatory M1 are round and M2 anti-inflammatory macrophages are elongated. We showed previously that interference with RhoA pathway (RhoA deletion or RhoA/ROCK kinase inhibition) disrupted actin, produced extremely elongated (hummingbird) macrophage phenotype and inhibited macrophage movement toward transplanted hearts...
October 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29045568/loss-of-protein-kinase-novel-1-pkn1-is-associated-with-mild-systolic-and-diastolic-contractile-dysfunction-increased-phospholamban-thr17-phosphorylation-and-exacerbated-ischaemia-reperfusion-injury
#5
Asvi A Francois, Kofo Obasanjo-Blackshire, James E Clark, Andrii Boguslavskyi, Mark R Holt, Peter Parker, Michael S Marber, Richard J Heads
Aims: PKN1 is a stress-responsive protein kinase acting downstream of small GTP-binding proteins of the Rho/Rac family. The aim was to determine its role in endogenous cardioprotection. Methods and Results: Hearts from PKN1 knockout (KO) or wild type (WT) littermate control mice were perfused in Langendorff mode and subjected to global ischemia and reperfusion (I/R). Myocardial infarct size was doubled in PKN1 KO hearts compared to WT hearts. PKN1 was basally phosphorylated on the activation loop Thr778 PDK1 target site which was unchanged during I/R...
October 16, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29029794/rho-kinase-inhibition-reverses-impaired-ca-2-handling-and-associated-left-ventricular-dysfunction-in-pressure-overload-induced-cardiac-hypertrophy
#6
Yusuf Olgar, Murat Cenk Celen, Bilge Eren Yamasan, Nihal Ozturk, Belma Turan, Semir Ozdemir
Recent studies have implicated a relationship between RhoA/ROCK activity and defective Ca(2+) homeostasis in hypertrophic hearts. This study investigated molecular mechanism underlying ROCK inhibition-mediated cardioprotection against pressure overload-induced cardiac hypertrophy, with a focus on Ca(2+) homeostasis. Cardiac hypertrophy model was established by performing transverse aortic constriction (TAC) in 8-week-old male rats. Groups were assigned as SHAM, TAC and TAC+Fas (rats undergoing TAC and treated with fasudil)...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/28993547/development-of-novel-therapies-for-cardiovascular-diseases-by-clinical-application-of-basic-research
#7
Kimio Satoh
Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells, inflammatory cells, activated platelets, and cardiac fibroblasts in response to oxidative stress. Excessive and continuous activation of the RhoA/Rho-kinase system promotes the secretion of CyPA, resulting in the development of multiple cardiovascular diseases. Basigin (Bsg), a transmembrane glycoprotein that activates matrix metalloproteinases, is an extracellular receptor for CyPA that promotes cell proliferation and inflammation. Thus, the CyPA/Bsg system is potentially a novel therapeutic target for cardiovascular diseases...
October 6, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28928610/does-heart-type-fatty-acid-binding-protein-predict-clinical-outcomes-after-pediatric-cardiac-surgery
#8
Egmond S Evers, Varsha Walavalkar, Suresh Pujar, Latha Balasubramanian, Frits W Prinzen, Tammo Delhaas, Ward Y Vanagt, Shreesha Maiya
INTRODUCTION: The early identification of vulnerable pediatric cardiac surgery patients can help clinicians provide them with timely support. Heart-type fatty acid-binding protein. (H-FABP) is an early biomarker of myocardial injury in acute myocardial infarction in adults. In this study, we evaluated the correlations between postoperative H-FABP, creatine kinase-myocardial band (CK-MB), troponin-I, total bypass time, and clinical outcomes. METHODS: In 32 pediatric patients that underwent ventricular septal defect...
September 2017: Annals of Pediatric Cardiology
https://www.readbyqxmd.com/read/28818859/renal-denervation-suppresses-coronary-hyperconstricting-responses-after-drug-eluting-stent-implantation-in-pigs-in-vivo-through-the-kidney-brain-heart-axis
#9
Hironori Uzuka, Yasuharu Matsumoto, Kensuke Nishimiya, Kazuma Ohyama, Hideaki Suzuki, Hirokazu Amamizu, Susumu Morosawa, Michinori Hirano, Tomohiko Shindo, Yoku Kikuchi, Kiyotaka Hao, Takashi Shiroto, Kenta Ito, Jun Takahashi, Koji Fukuda, Satoshi Miyata, Yoshihito Funaki, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Hiroaki Shimokawa
OBJECTIVE: Drug-eluting stent-induced coronary hyperconstricting responses remain an important issue. The adventitia harbors a variety of components that potently modulate vascular tone, including sympathetic nerve fibers (SNF) and vasa vasorum. Catheter-based renal denervation (RDN) inhibits sympathetic nerve activity. We, thus, examined whether RDN suppresses drug-eluting stent-induced coronary hyperconstricting responses, and if so, what mechanisms are involved. APPROACH AND RESULTS: Protocol 1: pigs implanted with everolimus-eluting stents into the left coronary arteries underwent coronary angiography at 1 month after implantation for assessment of coronary vasomotion and adventitial SNF formation...
October 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28739304/role-of-nadphox-rho-kinase-signaling-in-the-cyclosporine-nsaids-interactions-on-blood-pressure-and-baroreflexes-in-female-rats
#10
Hanan M El-Gowelli, Karim S Ibrahim, Ahmed F El-Yazbi, Mahmoud M El-Mas
AIMS: The hypertensive effect of the immunosuppressant drug cyclosporine (CSA) is paralleled, and probably triggered, by impaired arterial baroreceptor sensitivity (BRS). Here we asked if these effects of CSA are influenced by co-administration of nonsteroidal antiinflammatory drugs (NSAIDs) and if the oxidative NADPH-oxidase (NADPHox)/Rho-kinase (ROCK) pathway mediates this interaction. MATERIALS AND METHODS: Female rats were treated for 10days with CSA (25mg/kg/day), diclofenac (DIC, COX-1/COX-2 inhibitor, 1mg/kg/day), celecoxib (COX-2 inhibitor, 10mg/kg/day), or their combinations...
July 21, 2017: Life Sciences
https://www.readbyqxmd.com/read/28712398/-fasudil-attenuates-mitochondrial-injury-and-apoptosis-in-rat-model-of-myocardial-ischemia-reperfusion-injury
#11
Hongwei Ye, Guanjun Zhang, Ruiping Cao, Pinfang Kang, Zhenghong Li, Qin Gao
Objective To observe the changes of mitochondria fusion protein 2 (Mfn2) and dynamin-related protein 1 (Drp1) in the cardioprotection of fasudil, and analyze the significance. Methods Hearts isolated from male Sprague-Dawley rats were subjected to ischemia for 30 minutes (occlusion of left anterior descending artery), and continuously perfusion for 120 minutes to establish myocardial ischemia/reperfusion (I/R) injury model. The rats were divided into 3 groups: sham group, I/R group and fasudil group. The left ventricular hemodynamics were continuously recorded; lactate dehydrogenase (LDH) content was measured during reperfusion; myocardial ultrastructure was observed by electron microscopy; the protein expression of phosphorylated protein phosphatase 1 regulatory subunit 12A (p-PPP1R12A/p-MYPT1) was detected by immunohistochemistry; and the protein expressions of Mfn2, Drp1 and cleaved caspase-3 (c-caspase-3) were detected by Western blot analysis...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28679962/fibroblast-deletion-of-rock2-attenuates-cardiac-hypertrophy-fibrosis-and-diastolic-dysfunction
#12
Toru Shimizu, Nikhil Narang, Phetcharat Chen, Brian Yu, Maura Knapp, Jyothi Janardanan, John Blair, James K Liao
Although left ventricular (LV) diastolic dysfunction is often associated with hypertension, little is known regarding its underlying pathophysiological mechanism. Here, we show that the actin cytoskeletal regulator, Rho-associated coiled-coil containing kinase-2 (ROCK2), is a critical mediator of LV diastolic dysfunction. In response to angiotensin II (Ang II), mutant mice with fibroblast-specific deletion of ROCK2 (ROCK2Postn-/-) developed less LV wall thickness and fibrosis, along with improved isovolumetric relaxation...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28657365/acute-hypobaric-hypoxia-augments-rock2-protein-level-and-activity
#13
Priyanka Pandey, Sangeeta Kumari, Zahara Ali, Ma Qadar Pasha
AIM: Rho kinase activation plays an important role in hypoxic pulmonary vasoconstriction and increased vascular resistance. The present study investigated changes in the level and activity of rho kinase isoform 2 (ROCK2) under acute hypobaric hypoxia exposure. For this, Wistar rats were taken as the model organism. MATERIALS AND METHODS: Fifteen male Wistar rats (4-6 week old, 250 grams) were normalized with the surrounding environment by providing a 12/12 hour day and night acclimatization cycle...
May 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28589995/trans-polydatin-protects-the-mouse-heart-against-ischemia-reperfusion-injury-via-inhibition-of-the-renin-angiotensin-system-ras-and-rho-kinase-rock-activity
#14
Dong Ming, Liao Songyan, Chen Yawen, Zheng Na, Ma Jing, Xiao Zhaowen, Liu Ye, Ding Wa, Liu Jie
BACKGROUND: Recent studies highlighted the protective benefits of a Chinese herb extract from polygonum cuspidatum, trans-polydatin, on cardiac disease. We investigated the therapeutic effect of trans-polydatin on myocardial ischemia/reperfusion (IR) injury and the underlying mechanisms related to the renin-angiotensin system (RAS) and RhoA kinase (ROCK) pathway. METHODS AND RESULTS: Experiments were performed on neonatal rats' ventricular myocytes that were subjected to hypoxia-reoxygenation (simulated IR, SIR) and on adult mice which were subjected to left anterior descending coronary artery occlusion for 45 min followed by a one-week reperfusion...
June 21, 2017: Food & Function
https://www.readbyqxmd.com/read/28575410/enhanced-endothelin-1-rho-kinase-signalling-and-coronary-microvascular-dysfunction-in-hypertensive-myocardial-hypertrophy
#15
Shu-Huai Tsai, Guangrong Lu, Xin Xu, Yi Ren, Travis W Hein, Lih Kuo
Aims: Hypertensive cardiac hypertrophy is associated with reduced coronary flow reserve, but its impact on coronary flow regulation and vasomotor function remains incompletely understood and requires further investigation. Methods and results: Left ventricular hypertrophy was induced in mice by transverse aortic coarctation (TAC) for 4 weeks. The left coronary artery blood velocity (LCABV) and myocardium lactate level were measured following the metabolic activation by isoproterenol...
September 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28484504/effect-of-qskl-on-mapk-and-rhoa-pathways-in-a-rat-model-of-heart-failure
#16
Kai Xia, Qiyan Wang, Chun Li, Zifan Zeng, Yong Wang, Wei Wang
Qishenkeli (QSKL) is one of the Chinese medicine formulae for treating heart failure and has been shown to have an antifibrotic effect. However, the mechanism of its therapeutic effects remains unclear. In this study, we aimed to explore whether QSKL could exert an antifibrotic effect by attenuating ras homolog family member A (RhoA) and mitogen activated protein kinase (MAPK) pathways. Rats were randomly divided into sham group, model group, QSKL group, and positive control group. Heart failure was induced by ligation of the left ventricle anterior descending artery...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28416371/modulation-by-nadph-oxidase-of-the-chronic-cardiovascular-and-autonomic-interaction-between-cyclosporine-and-nsaids-in-female-rats
#17
Ahmed F El-Yazbi, Karim S Ibrahim, Hanan M El-Gowelli, Nevine M El-Deeb, Mahmoud M El-Mas
Cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) are used together to manage arthritic disorders with an immune component. Previous reports showed contrasting effects for NSAIDs on CSA nephrotoxicity and acute elevations in blood pressure. Both effects were ameliorated or exaggerated after selective cyclooxygenase-2 (COX2) and nonselective COX inhibition, respectively. Here we investigated: (i) the interaction of CSA with NSAIDs possessing variable COX1/COX2 selectivities on hemodynamic, left ventricular (LV) and cardiac autonomic and histologic profiles, and (ii) role of NADPH-oxidase (NOX)/Rho-kinase (ROCK) pathway in the interaction...
April 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28400117/phosphatidylinositol-3-kinase-inhibition-induces-vasodilator-effect-of-sevoflurane-via-reduction-of-rho-kinase-activity
#18
Yasunori Miyamoto, Guo-Gang Feng, Shiho Satomi, Katsuya Tanaka, Yoshihiro Fujiwara, Hiroyuki Kinoshita
AIMS: This study was aimed to examine whether a volatile anesthetic sevoflurane in clinical doses reduces vasoconstriction under the inhibition of phosphatidylinositol 3-kinase (PI3K) in the rat and human arteries and whether the intravenous administration of the PI3K inhibitor decreases blood pressure in rats under the sevoflurane inhalation. MATERIALS AND METHODS: Rat arteries (n=5-6) and human omental arteries (n=5-6) were subjected to isometric force recordings and western immunoblotting for Rho kinase, mitogen-activated protein kinase, and protein kinase C...
May 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28183205/inhibition-of-rho-kinase-protects-from-ischaemia-reperfusion-injury-via-regulation-of-arginase-activity-and-nitric-oxide-synthase-in-type-1-diabetes
#19
Yahor Tratsiakovich, Attila Kiss, Adrian T Gonon, Jiangning Yang, Per-Ove Sjöquist, John Pernow
AIM: RhoA/Rho-associated kinase and arginase are implicated in vascular complications in diabetes. This study investigated whether RhoA/Rho-associated kinase and arginase inhibition protect from myocardial ischaemia-reperfusion injury in type 1 diabetes and the mechanisms behind these effects. METHODS: Rats with streptozotocin-induced type 1 diabetes and non-diabetic rats were subjected to 30 min myocardial ischaemia and 2 h reperfusion after being randomized to treatment with (1) saline, (2) RhoA/Rho-associated kinase inhibitor hydroxyfasudil, (3) nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine monoacetate followed by hydroxyfasudil, (4) arginase inhibitor N-omega-hydroxy-nor-l-arginine, (5) N(G)-monomethyl-l-arginine monoacetate followed by N-omega-hydroxy-nor-l-arginine or (6) N(G)-monomethyl-l-arginine monoacetate given intravenous before ischaemia...
May 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28165252/cocktail-of-superoxide-dismutase-and-fasudil-encapsulated-in-targeted-liposomes-slows-pah-progression-at-a-reduced-dosing-frequency
#20
Nilesh Gupta, Jahidur Rashid, Eva Nozik-Grayck, Ivan F McMurtry, Kurt R Stenmark, Fakhrul Ahsan
Currently, two or more pulmonary vasodilators are used to treat pulmonary arterial hypertension (PAH), but conventional vasodilators alone cannot reverse disease progression. In this study, we tested the hypothesis that a combination therapy comprising a vasodilator plus a therapeutic agent that slows pulmonary arterial remodeling and right heart hypertrophy is an efficacious alternative to current vasodilator-based PAH therapy. Thus, we encapsulated a cocktail of superoxide dismutase (SOD), a superoxide scavenger, and fasudil, a specific rho-kinase inhibitor, into a liposomal formulation equipped with a homing peptide, CAR...
March 6, 2017: Molecular Pharmaceutics
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