Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently a FES (functional electrical stimulation)-assisted rowing machine was developed to enhance cardiovascular training in people with spinal cord injuries. The machine was assessed in terms of its efficacy as a training tool. Six patients who were quadriplegic (C6-T1) and 2 who were paraplegic (T3-6) completed a series of three tests in succession: (1) leg stimulation only (quadriceps and hamstring groups)--'Stim', (2) arm row only--'Row' and (3) simultaneous row and stimulation--'R & S'. Measurements recorded included oxygen uptake (VO2), minute ventilation (Ve), respiratory exchange ratio (RER), heart rate (HR) and blood pressure (BP). In addition, 6 out of the 8 subjects took part in a qualitative assessment comprising a guided interview exploring the subject's perception of the machine and test. Significant increases in VO2 were demonstrated between the three tests with R & S producing mean steady-state values of 16.34 nm (+/- 0.74) ml/kg/min (83% of maximum). These values represented a 12% increase over Row alone. Of interest was the qualitative assessment which revealed that subjects perceived R & S to be easier than Row despite the higher levels of VO2 observed. The results suggest that the rowing machine represents a potentially valuable hybrid training device that may significantly reduce risk factors for cardiovascular disease and improve the quality of life of people with SCI.
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PMID:Electrical stimulation-assisted rowing exercise in spinal cord injured people. A pilot study. 841 39

Angiotensin II (AII), acting via its G-protein linked receptor, is an important regulator of cardiac, vascular, and renal function. Following injection of AII into rats, we find that there is also a rapid tyrosine phosphorylation of the major insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in the heart. This phenomenon appears to involve JAK2 tyrosine kinase, which associates with the AT1 receptor and IRS-1/IRS-2 after AII stimulation. AII-induced phosphorylation leads to binding of phosphatidylinositol 3-kinase (PI 3-kinase) to IRS-1 and IRS-2; however, in contrast to other ligands, AII injection results in an acute inhibition of both basal and insulin-stimulated PI 3-kinase activity. The latter occurs without any reduction in insulin receptor or IRS phosphorylation or in the interaction of the p85 and p110 subunits of PI 3-kinase with each other or with IRS-1/IRS-2. These effects of AII are inhibited by AT1 receptor antagonists. Thus, there is direct cross-talk between insulin and AII signaling pathways at the level of both tyrosine phosphorylation and PI 3-kinase activation. These interactions may play an important role in the association of insulin resistance, hypertension, and cardiovascular disease.
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PMID:Cross-talk between the insulin and angiotensin signaling systems. 890 9

A number of safe and effective contraceptive choices exist for the perimenopausal woman. With increasing experience, we have learned that hormonal methods are safer than initially thought, particularly with the lower-dose formulations currently prescribed. Furthermore, the pill offers many noncontraceptive health benefits. And while progestins, in contraceptive doses, have a slight adverse impact on the lipoprotein profile, there has been no parallel increase in clinical cardiovascular disease. Since elimination of the Dalkon shield, the IUD has been recognized as a very safe and effective method of contraception; the risk of associated infection seems primarily related to the insertion procedure. Barrier methods provide somewhat reliable contraception, with varying degrees of added protection against STD. The decreased fertility rate among perimenopausal women allows some latitude when contraceptive methods with suboptimal efficacies are selected; however, unintended pregnancy is a significant problem for women older than 40 years, should it occur. Surgical sterilization remains the most popular form of contraception among perimenopausal-aged couples. Natural family planning techniques are safe and somewhat underutilized. All women should be counseled about the availability of postcoital contraceptive methods.
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PMID:Contraceptive Options for Perimenopausal Women. 974 40

The increase in vascular wall stress imposed by hypertension has been strongly implicated in the pathogenesis of cardiovascular disease. Much of this chronic cyclical mechanical strain is experienced by the vascular smooth (VSM) cells of the vascular media. The cellular mechanisms whereby VSM cells sense and respond to changing mechanical forces are poorly understood. This review focuses on an emerging field of cardiovascular research in which the direct effects of mechanical strain on VSM cells and isolated blood vessels in organ culture have been characterized, in vitro. Cyclical mechanical strain profoundly influences cultured VSM cell orientation, growth and phenotype. Mechanical strain also increases the secretory function of VSM cells leading to increased extracellular matrix protein production. Vasoactive mediators such as angiotensin II potentiate these effects. Mechanical strain increases VSM cell release of platelet derived growth factor, transforming growth factor beta1, fibroblast growth factor and vascular endothelial growth factor, which act in autocrine or paracrine loops to influence VSM and endothelial cell growth and function. Mechanical strain may also activate local tissue renin-angiotensin systems and regulate expression of angiotensin II receptors within the cardiovascular system. The mechanism whereby VSM cells transduce mechanical stimuli into an intracellular signal and biological response, i.e. 'mechanotransduction', is strongly dependent on integrins. Moreover, specific matrix protein:integrin engagements lead to differential VSM cells responses via the selective activation of numerous intracellular signalling pathways including; mitogen-activated protein kinase, focal adhesion kinase and c-Src. The study of vascular mechanotransduction has begun to delineate the complex cellular basis of cardiovascular structural and functional modification in hypertension.
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PMID:Mechanical influences on vascular smooth muscle cell function. 988 78

In this review, the signal events regulated by angiotensin II (AngII) in vascular smooth muscle are analyzed based on activation of specific tyrosine kinases. AngII has been shown to play a critical role in the pathogenesis of hypertension, inflammation, atherosclerosis, and congestive heart failure. The expanding role of AngII indicates that multiple signal transduction pathways are likely to be activated in a tissue-specific manner. Although at least three AngII receptors have been characterized, it seems that the AngII type I receptor (AT1R) is physiologically most important since pharmacologic inhibitors of the AT1R block most AngII signal events and have beneficial effects on cardiovascular disease. The AT1R is a seven transmembrane-spanning G protein-coupled receptor that regulates intracellular signal events by activation of Gq and Gi. However, many recent data indicate that activation of tyrosine kinases by several different mechanisms contributes to AngII effects in target tissues. Tyrosine kinases activated by AngII include c-Src, focal adhesion kinase (FAK), Pyk2 (CADTK), Janus kinases (JAK2 and TYK2), and the receptor tyrosine kinases Ax1, epidermal growth factor, and platelet-derived growth factor. Finally, unknown tyrosine kinases may mediate tyrosine phosphorylation of paxillin, Shc, Raf, and phospholipase C-gamma after AngII stimulation. These AngII-regulated tyrosine kinases seem to be required for AngII effects such as vasoconstriction, proto-oncogene expression, and protein synthesis based on studies with tyrosine kinase inhibitors. Thus, understanding AngII-stimulated signaling events, especially those related to tyrosine kinase activity, may form the basis for the development of new therapies for cardiovascular diseases.
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PMID:Angiotensin II signal transduction in vascular smooth muscle: pathways activated by specific tyrosine kinases. 989 42

Reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O(2)) activate intracellular signal transduction pathways implicated in the pathogenesis of cardiovascular disease. H(2)O(2) is a mitogen for rat vascular smooth muscle cells (VSMCs), and protein tyrosine phosphorylation is a critical event in VSMC mitogenesis. Therefore, we investigated whether the mitogenic effects of H(2)O(2), such as stimulation of extracellular signal-regulated kinase (ERK)2, are mediated via activation of cytoplasmic Janus tyrosine kinases (JAKs). JAK2 was activated rapidly in VSMCs treated with H(2)O(2), and signal transducers and activators of transcription (STAT) STAT1 and STAT3 were tyrosine-phosphorylated and translocated to the nucleus in a JAK2-dependent manner. Inhibition of JAK2 activity with AG-490 partially inhibited H(2)O(2)-induced ERK2 activity, suggesting that JAK2 is upstream of the Ras/Raf/mitogen-activated protein kinase-ERK/ERK mitogenic pathway. Because heat-shock proteins (HSPs) can protect cells from ROS, we investigated the effect of H(2)O(2) on HSP expression. H(2)O(2) stimulated HSP70 expression in a time-dependent manner, and AG-490 abolished H(2)O(2)-induced HSP70 expression. H(2)O(2) activated the HSP70 promoter via enhanced binding of STATs to cognate binding sites in the promoter. Regulation of chaperones such as HSP70 via activation of the JAK/STAT pathway suggests that in addition to its growth-promoting effects, this pathway may help VSMCs adapt to oxidative stress.
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PMID:Reactive oxygen species regulate heat-shock protein 70 via the JAK/STAT pathway. 1123 9

Enhanced production of reactive oxygen species (ROS) such as H(2)O(2) and a failure in ROS removal by scavenging systems are hallmarks of several cardiovascular diseases such as atherosclerosis and hypertension. ROS act as second messengers that play a prominent role in intracellular signaling and cellular function. In vascular smooth muscle cells (VSMCs), a vascular pathogen, angiotensin II, appears to initiate growth-promoting signal transduction through ROS-sensitive tyrosine kinases. However, the precise mechanisms by which tyrosine kinases are activated by ROS remain unclear. In this review, the current knowledge that suggests how certain tyrosine kinases are activated by ROS, along with their functional significance in VSMCs, will be discussed. Recent findings suggest that transactivation of the epidermal growth factor receptor by ROS requires metalloprotease-dependent heparin-binding epidermal growth factor-like growth factor production, whereas other ROS-sensitive tyrosine kinases such as PYK2, JAK2, and platelet-derived growth factor receptor require activation of protein kinase C-delta. Each of these ROS-sensitive kinases could mediate specific signaling critical for pathophysiological responses. Detailed analysis of the mechanism of cross-talk and the downstream function of these various tyrosine kinases will yield new therapeutic interventions for cardiovascular disease.
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PMID:Activation of tyrosine kinases by reactive oxygen species in vascular smooth muscle cells: significance and involvement of EGF receptor transactivation by angiotensin II. 1458 50

Lipoprotein(a) is an important predictor of cardiovascular disease risk. The lack of internationally accepted standardization has impeded the broad application of this lipoprotein in laboratory medicine. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC), through its Working Group on Lipoprotein(a) and together with research institutions and several diagnostic companies, have succeeded in developing an international reference material that is intended for the transfer of a lipoprotein(a) concentration to manufacturers' master calibrators. IFCC SRM 2B has recently been accepted by the WHO Expert Committee on Biological Standardization as the 'First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay'. The assigned unitage of 0.1071 nanomoles of lipoprotein(a) per vial is traceable to the consensus reference method for lipoprotein(a) and will enable conformity by diagnostic companies to the European Union's Directive on In vitro Diagnostic Medical Devices for the metrological traceability of calibrator materials.
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PMID:First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay--Lp(a) SRM 2B. 1525 85

Platelet-leukocyte conjugates are increased in cardiovascular disease, but exercise is also able to trigger platelet-leukocyte formation in healthy subjects. The aim was to investigate the heterogeneity of platelet-leukocyte conjugate formations triggered by short term exercise. 18 healthy non-smokers underwent a 90 second maximal test on a SRM cycle ergometry system and a control experiment. Blood samples were taken after 30 min rest, immediately before and after, 15 min and 1 h after exercise. The different platelet-leukocyte conjugates were detected by flow cytometry via CD45, CD14, CD16, CD41, together with CD62P antibodies for the investigation of platelet activation in the conjugates. In addition, a stimulation of conjugate formation in vitro with 8 microM TRAP-6 was initiated. Immediately after exercise platelet-granulocyte (+24%), and -lymphocyte (+17%) conjugates were increased (p<0.01), while the platelet-monocyte conjugates (+40%) were enhanced (p<0.05) 15 min after exercise. The differentiation after stimulation showed that the regular (CD14(+)16(-); +32%) and mature (CD14(+)16(+); +35%) monocytes were both increased after exercise (p<0.01) but the regular monocytes were preferred (p<0.001) in platelet-monocyte conjugate formation. In addition, these conjugates revealed the highest CD62P expression. Maximal short term exercise is useful for the investigation of platelet-leukocyte formation; e.g., it could be shown, that regular monocytes may be preferred in conjugate formation and that these conjugates revealed the highest CD62P expression.
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PMID:Differentiation of platelet-leukocyte conjugate formation by short term exercise. 1532 27

A chronic increase in systemic levels of acute-phase reactants contributes to the development of insulin resistance and associated disorders such as cardiovascular disease. Recently, serum amyloid A3 (SAA3) has been characterized as an adipocyte-secreted acute-phase reactant, expression of which is dramatically increased in insulin resistance and obesity. To further clarify expression and regulation of this adipocytokine in fat, SAA3 mRNA was measured by quantitative real-time reverse transcriptase PCR during differentiation of 3T3-L1 adipocytes and after treatment with various hormones known to induce insulin resistance and contribute to atherosclerosis. SAA3 mRNA was dramatically induced up to 77-fold during differentiation of 3T3-L1 preadipocytes. Furthermore, 100 nM dexamethasone and 30 ng/ml interleukin (IL)-6 induced SAA3 mRNA by up to 11- and 4.8-fold, respectively, in a time-dependent fashion with significant stimulation observed at concentrations as low as 10 nM dexamethasone and 1 ng/ml IL-6. In contrast, insulin, isoproterenol and growth hormone did not influence SAA3 synthesis. Inhibitor studies suggested that the positive effect of IL-6 on SAA3 expression is at least in part mediated by Janus kinase 2. Taken together, our results show a differential regulation of SAA3 by glucocorticoids and IL-6 supporting an integrative role of this acute-phase reactant in the pathogenesis of insulin resistance and its link to obesity and cardiovascular disease.
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PMID:Serum amyloid A3 expression is stimulated by dexamethasone and interleukin-6 in 3T3-L1 adipocytes. 1559 Sep 82


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