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https://www.readbyqxmd.com/read/27780848/sucrose-non-fermenting-related-kinase-enzyme-mediated-rho-associated-kinase-signaling-is-responsible-for-cardiac-function
#1
Stephanie M Cossette, Vijesh J Bhute, Xiaoping Bao, Leanne M Harmann, Mark A Horswill, Indranil Sinha, Adam Gastonguay, Shabnam Pooya, Michelle Bordas, Suresh N Kumar, Shama P Mirza, Sean Palecek, Jennifer Strande, Ramani Ramchandran
BACKGROUND: -Cardiac metabolism is critical for the functioning of the heart, and disturbance in this homeostasis is likely to influence cardiac disorders or cardiomyopathy. Our lab has previously shown that sucrose non-fermenting related kinase (SNRK) enzyme, which belongs to the AMP-activated kinase (AMPK) family, was essential for cardiac metabolism in mammals. Snrk global homozygous knockout (KO) mice die at postnatal day 0, and conditional deletion of Snrk in cardiomyocytes (Snrk cmcKO) leads to cardiac failure, and death by 8-10 months...
October 25, 2016: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/27753928/os-05-03-decreased-rho-kinase-based-calcium-sensitization-in-hypertensive-ren-2-transgenic-rats-tgr
#2
Josef Zicha, Michal Behuliak, Ivana Vaneckova
OBJECTIVE: Comparing BP response to Ca channel opener BAY K8644 prior and after Rho kinase inhibition we demonstrated lowered calcium sensitization in spontaneously hypertensive rats (SHR), although BP response of intact SHR to Rho kinase inhibitor fasudil was enhanced (Behuliak et al. J Hypertens 31:2025,2013). The aim of the present study was to evaluate calcium sensitization in hypertensive TGR and their normotensive HanSD controls using the same methods. We also tried to elucidate the interference of baroreflex-activated sympathetic activity with BP response to fasudil...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27672026/central-angiotensin-ii-increases-blood-pressure-and-sympathetic-outflow-via-rho-kinase-activation-in-conscious-rabbits
#3
Peter R Pellegrino, Alicia M Schiller, Karla K V Haack, Irving H Zucker
Elevated sympathetic tone and activation of the renin-angiotensin system are pathophysiologic hallmarks of hypertension, and the interactions between these systems are particularly deleterious. The importance of Rho kinase as a mediator of the effects of angiotensin-II (AngII) in the periphery is clear, but the role of Rho kinase in sympathoexcitation caused by central AngII is not well established. We hypothesized that AngII mediates its effects in the brain by the activation of the RhoA/Rho kinase pathway...
November 2016: Hypertension
https://www.readbyqxmd.com/read/27643321/os-05-03-decreased-rho-kinase-based-calcium-sensitization-in-hypertensive-ren-2-transgenic-rats-tgr
#4
Josef Zicha, Michal Behuliak, Ivana Vaneckova
OBJECTIVE: Comparing BP response to Ca channel opener BAY K8644 prior and after Rho kinase inhibition we demonstrated lowered calcium sensitization in spontaneously hypertensive rats (SHR), although BP response of intact SHR to Rho kinase inhibitor fasudil was enhanced (Behuliak et al. J Hypertens 31:2025,2013). The aim of the present study was to evaluate calcium sensitization in hypertensive TGR and their normotensive HanSD controls using the same methods. We also tried to elucidate the interference of baroreflex-activated sympathetic activity with BP response to fasudil...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27581840/liraglutide-prevents-and-reverses-monocrotaline-induced-pulmonary-arterial-hypertension-by-suppressing-et-1-and-enhancing-enos-sgc-pkg-pathways
#5
Mei-Yueh Lee, Kun-Bow Tsai, Jong-Hau Hsu, Shyi-Jang Shin, Jiunn-Ren Wu, Jwu-Lai Yeh
Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, is widely used to treat diabetes. However, its effect on pulmonary arterial hypertension (PAH) is unknown. In this study, we investigated its effects on rats with monocrotaline (MCT)-induced PAH and mechanisms on rat pulmonary artery smooth muscle cells (PASMCs). Liraglutide was investigated for both prevention and treatment of MCT-induced PAH. The hemodynamic and body weight changes, right heart hypertrophy, lung morphology, immune-reactivity of endothelial nitric oxide synthase (eNOS), endothelin-1 and cyclic guanosine monophosphate (cGMP) levels, protein expressions of eNOS, soluble guanylyl cyclase (sGCα), protein kinase G (PKG) and Rho kinase (ROCK) II pathway were measured in both in vivo and in vitro...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27576917/the-rho-kinase-inhibitor-fasudil-ameliorates-diabetes-induced-cardiac-dysfunction-by-improving-calcium-clearance-and-actin-remodeling
#6
Dongwu Lai, Jing Gao, Xukun Bi, Hong He, Xiaolu Shi, Shaoxiang Weng, Yu Chen, Ying Yang, Yang Ye, Guosheng Fu
: Previous study showed inhibition of RhoA and Rho kinase (ROCK) activity with fasudil could alleviate diabetes-induced cardiac dysfunction partially due to improvement of myocardial fibrosis. However, the effect of fasudil on intracellular calcium cycling and actin remodeling, both of which are important to regulate excitation-contract coupling, is still not fully elucidated. In this study, a diabetic cardiomyopathy model was induced by a single intraperitoneal injection of streptozotocin (STZ) in male Sprague Dawley rats...
August 30, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27565218/inhibition-of-rhoa-rho-kinase-by-ibuprofen-exerts-cardioprotective-effect-on-isoproterenol-induced-myocardial-infarction-in-rats
#7
Prexita Patel, Mihir Parikh, Hital Shah, Tejal Gandhi
Myocardial infarction (MI) and hypertension are the leading cause of death worldwide so protection of heart is focus of intense research. Rho-kinase, a downstream effector of protein involved in MI and hypertension, is inhibited by ibuprofen. This study aims to elucidate cardioprotective effect of ibuprofen in rats. MI was produced in rats with 85mg/kg isoproterenol (ISO) administered s.c. twice at an interval of 24h. The rats were randomized into six groups: (I) Normal; (II) ISO; (III) ISO + ascorbic acid (250mg/kg p...
August 23, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27534880/hypoxia-induced-contraction-of-chicken-embryo-mesenteric-arteries-mechanisms-and-developmental-changes
#8
Leonie Brinks, Rob Mj Moonen, Javier Moral-Sanz, Bianca Barreira, Lilian Kessels, Francisco Perez-Vizcaino, Angel Cogolludo, Eduardo Villamor
The fetal cardiovascular responses to acute hypoxia includes a redistribution of the cardiac output towards the heart and the brain at the expense of other organs, such as the intestine. We hypothesized that hypoxia exerts a direct effect on the mesenteric artery (MA) that may contribute to this response. Using wire myography, we investigated the response to hypoxia (Po2 ~2.5 kPa for 20 min) of isolated MAs from 15- to 21-d chicken embryos (E15, E19 E21), and 1- to 45-d-old chickens (P1, P3, P14, P45). Agonist-induced pretone or an intact endothelium were not required to obtain a consistent and reproducible response to hypoxia, which showed a pattern of initial rapid phasic contraction followed by a sustained tonic contraction...
August 17, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27515283/phos-tag-sds-page-resolves-agonist-and-isoform-specific-activation-patterns-for-pkd2-and-pkd3-in-cardiomyocytes-and-cardiac-fibroblasts
#9
Weihua Qiu, Susan F Steinberg
Protein kinase D (PKD) consists of a family of three structurally related enzymes that are co-expressed in the heart and have important roles in many biological responses. PKD1 is activated by pro-hypertrophic stimuli and has been implicated in adverse cardiac remodeling. Efforts to define the cardiac actions of PKD2 and PKD3 have been less successful at least in part because conventional methods provide a general screen for PKD activation but are poorly suited to resolve activation patterns for PKD2 or PKD3...
October 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27388289/the-effects-and-mechanism-of-atorvastatin-on-pulmonary-hypertension-due-to-left-heart-disease
#10
Qing Wang, Yi-Zhan Guo, Yi-Tao Zhang, Jiao-Jie Xue, Zhi-Chong Chen, Shi-Yao Cheng, Mao-De Ou, Kang-Lin Cheng, Wei-Jie Zeng
BACKGROUND: Pulmonary hypertension due to left heart disease (PH-LHD) is one of the most common forms of PH, termed group 2 PH. Atorvastatin exerts beneficial effects on the structural remodeling of the lung in ischemic heart failure. However, few studies have investigated the effects of atorvastatin on PH due to left heart failure induced by overload. METHODS: Group 2 PH was induced in animals by aortic banding. Rats (n = 20) were randomly divided into four groups: a control group (C), an aortic banding group (AOB63), an atorvastatin prevention group (AOB63/ATOR63) and an atorvastatin reversal group (AOB63/ATOR50-63)...
2016: PloS One
https://www.readbyqxmd.com/read/27334702/focused-proteomics-revealed-a-novel-rho-kinase-signaling-pathway-in-the-heart
#11
Yoshimitsu Yura, Mutsuki Amano, Mikito Takefuji, Tomohiro Bando, Kou Suzuki, Katsuhiro Kato, Tomonari Hamaguchi, Md Hasanuzzaman Shohag, Tetsuya Takano, Yasuhiro Funahashi, Shinichi Nakamuta, Keisuke Kuroda, Tomoki Nishioka, Toyoaki Murohara, Kozo Kaibuchi
Protein phosphorylation plays an important role in the physiological regulation of cardiac function. Myocardial contraction and pathogenesis of cardiac diseases have been reported to be associated with adaptive or maladaptive protein phosphorylation; however, phosphorylation signaling in the heart is not fully elucidated. We recently developed a novel kinase-interacting substrate screening (KISS) method for exhaustive screening of protein kinase substrates, using mass spectrometry and affinity chromatography...
August 23, 2016: Cell Structure and Function
https://www.readbyqxmd.com/read/27320957/increased-rho-kinase-activity-predicts-worse-cardiovascular-outcome-in-st-segment-elevation-myocardial-infarction-patients
#12
Xiaohui Li, Xing Wu, Hongwei Li, Hui Chen, Yongliang Wang, Weiping Li, Xiaosong Ding, Xu Hong
BACKGROUND: Few clinical studies have assessed Rho kinase (ROCK) in patients with dia-betes mellitus (DM) and ST-segment elevation myocardial infarction (STEMI). This study aimed to determine whether ROCK activity in circulating leukocytes is increased in STEMI patients with DM and whether ROCK activity predicts the onset of cardiovascular events. METHODS: Blood samples were collected from 60 STEMI patients, divided into non-diabetes mellitus (NDM) and DM groups...
2016: Cardiology Journal
https://www.readbyqxmd.com/read/27312222/cadherin-11-overexpression-induces-extracellular-matrix-remodeling-and-calcification-in-mature-aortic-valves
#13
Derek C Sung, Caitlin J Bowen, Kiran A Vaidya, Jingjing Zhou, Nikita Chapurin, Andrew Recknagel, Bin Zhou, Jonathan Chen, Michael Kotlikoff, Jonathan T Butcher
OBJECTIVE: Calcific aortic valve (AoV) disease is a significant clinical problem for which the regulatory mechanisms are poorly understood. Enhanced cell-cell adhesion is a common mechanism of cellular aggregation, but its role in calcific lesion formation is not known. Cadherin-11 (Cad-11) has been associated with lesion formation in vitro, but its function during adult valve homeostasis and pathogenesis is not known. This study aims to elucidate the specific functions of Cad-11 and its downstream targets, RhoA and Sox9, in extracellular matrix remodeling and AoV calcification...
August 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27251065/rho-kinases-and-cardiac-remodeling
#14
Toru Shimizu, James K Liao
Hypertensive cardiac remodeling is characterized by left ventricular hypertrophy and interstitial fibrosis, which can lead to heart failure with preserved ejection fraction. The Rho-associated coiled-coil containing kinases (ROCKs) are members of the serine/threonine protein kinase family, which mediates the downstream effects of the small GTP-binding protein RhoA. There are 2 isoforms: ROCK1 and ROCK2. They have different functions in different types of cells and tissues. There is growing evidence that ROCKs contribute to the development of cardiovascular diseases, including cardiac fibrosis, hypertrophy, and subsequent heart failure...
June 24, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27225964/challenges-priorities-and-novel-therapies-for-hypoxemic-respiratory-failure-and-pulmonary-hypertension-in-the-neonate
#15
REVIEW
J L Aschner, J Gien, N Ambalavanan, J P Kinsella, G G Konduri, S Lakshminrusimha, O D Saugstad, R H Steinhorn
Future priorities for the management of hypoxemic respiratory failure (HRF) and pulmonary hypertension include primary prevention of neonatal lung diseases, 'precision medicine' and translating promising clinical and preclinical research into novel therapies. Promising areas of investigation include noninvasive ventilation strategies, emerging pulmonary vasodilators (for example, cinaciguat, intravenous bosentan, rho-kinase inhibitors, peroxisome proliferator-activated receptor-γ agonists) and hemodynamic support (arginine vasopressin)...
June 2016: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/27128553/simultaneous-rho-kinase-inhibition-in-circulating-leukocytes-and-in-cardiovascular-tissue-in-rats-with-high-angiotensin-converting-enzyme-levels
#16
Camila Fierro, Ulises Novoa, Veronica González, María Paz Ocaranza, Jorge E Jalil
BACKGROUND: The small guanosine triphosphatase RhoA and its direct target Rho kinase (ROCK) play important roles in cardiovascular pathophysiology. Activated ROCK phosphorylates intracellular proteins with detrimental effects on cardiovascular remodeling. Increased ROCK activity in circulating leukocytes is observed in hypertension and in heart failure, but its relationship with ROCK activation in the myocardium and vessels is unknown. We hypothesized that ROCK activation and phosphorylation/activation of some of its key downstream molecules in the heart and arterial wall are reflected in circulating leukocytes...
July 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27117132/oligophrenin1-protects-mice-against-myocardial-ischemia-and-reperfusion-injury-by-modulating-inflammation-and-myocardial-apoptosis
#17
Christina Niermann, Simone Gorressen, Meike Klier, Nina S Gowert, Pierre Billuart, Malte Kelm, Marc W Merx, Margitta Elvers
The Rho family of small GTPases has been analyzed in cardiac physiology and pathophysiology including myocardial infarction (MI) in the last years. Contradictory results show either a protective or a declined effect of RhoA and the RhoA effector Rho-associated protein kinase (ROCK) in myocardial ischemia and reperfusion injury that is associated with cardiomyocyte survival and caspase-3 activation. Cardiac-specific deletion of Rac1 reduced ischemia reperfusion injury in diabetic hearts, whereas cardiomyocyte specific overexpression of active Rac1 predisposes the heart to increased myocardial injury with enhanced contractile dysfunction...
August 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27080184/a-review-on-rock-ii-inhibitors-from-molecular-modelling-to-synthesis
#18
REVIEW
Surmil Shah, Jignasa Savjani
Rho kinase enzyme expressed in different disease conditions and involved in mediating vasoconstriction and vascular remodeling in the pathogenesis. There are two isoforms of Rho kinases, namely ROCK I and ROCK II, responsible for different physiological function due to difference in distribution, but almost similar in structure. The Rho kinase 2 belongs to AGC family and is widely distributed in brain, heart and muscles. It is responsible for contraction of vascular smooth muscles by calcium sensitization. Its defective and unwanted expression can lead to many medical conditions like multiple sclerosis, myocardial ischemia, inflammatory responses, etc...
May 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27050625/structure-based-design-synthesis-and-biological-evaluation-of-highly-selective-and-potent-g-protein-coupled-receptor-kinase-2-inhibitors
#19
Helen V Waldschmidt, Kristoff T Homan, Osvaldo Cruz-Rodríguez, Marilyn C Cato, Jessica Waninger-Saroni, Kelly M Larimore, Alessandro Cannavo, Jianliang Song, Joseph Y Cheung, Paul D Kirchhoff, Walter J Koch, John J G Tesmer, Scott D Larsen
G protein-coupled receptors (GPCRs) are central to many physiological processes. Regulation of this superfamily of receptors is controlled by GPCR kinases (GRKs), some of which have been implicated in heart failure. GSK180736A, developed as a Rho-associated coiled-coil kinase 1 (ROCK1) inhibitor, was identified as an inhibitor of GRK2 and co-crystallized in the active site. Guided by its binding pose overlaid with the binding pose of a known potent GRK2 inhibitor, Takeda103A, a library of hybrid inhibitors was developed...
April 28, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/26944323/phosphodiesterase-inhibitor-kmup-3-displays-cardioprotection-via-protein-kinase-g-and-increases-cardiac-output-via-g-protein-coupled-receptor-agonist-activity-and-ca-2-sensitization
#20
Chung-Pin Liu, Jwu-Lai Yeh, Shu-Fen Liou, Bin-Nan Wu, Ing-Jun Chen
KMUP-3 (7-{2-[4-(4-nitrobenzene) piperazinyl]ethyl}-1, 3-dimethylxanthine) displays cardioprotection and increases cardiac output, and is suggested to increase cardiac performance and improve myocardial infarction. To determine whether KMUP-3 improves outcomes in hypoperfused myocardium by inducing Ca(2+) sensitization to oppose protein kinase (PK)G-mediated Ca(2+) blockade, we measured left ventricular systolic blood pressure, maximal rates of pressure development, mean arterial pressure and heart rate in rats, and measured contractility and expression of PKs/RhoA/Rho kinase (ROCK)II in beating guinea pig left atria...
February 2016: Kaohsiung Journal of Medical Sciences
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