Abstract:
AIMS:Insulin (Ins) resistance (IRES) associates to increased cardiovascular risk as observed in metabolic syndrome. Chronic stimulation of beta-adrenergic receptors (betaAR) due to exaggerated sympathetic nervous system activity is involved in the pathogenesis of IRES. The cellular levels of G protein coupled receptor kinase 2 (GRK2) increase during chronic betaAR stimulation, leading to betaAR desensitization. We tested the hypothesis that GRK2 plays a role in betaAR-induced IRES. METHODS AND RESULTS:We evaluated Ins-induced glucose uptake and signalling responses in vitro in cell overexpressing the beta(2)AR, the GRK2, or the catalytically dead mutant GRK2-DN. In a model of increased adrenergic activity, IRES and elevated cellular GRK2 levels, the spontaneously hypertensive rats (SHR) we performed the intravenous glucose tolerance test load. To inhibit GRK2, we synthesized a peptide based on the catalytical sequence of GRK2 conjugated with the antennapedia internalization sequence (Ant-124). Ins in human kidney embryonic (HEK-293) cells causes rapid accumulation of GRK2, tyrosine phosphorylation of Ins receptor substrate 1 (IRS1) and induces glucose uptake. In the same cell type, transgenic beta(2)AR overexpression causes GRK2 accumulation associated with significant deficit of IRS1 activation and glucose uptake by Ins. Similarly, transgenic GRK2 overexpression prevents Ins-induced tyrosine phosphorylation of IRS1 and glucose uptake, whereas GRK2-DN ameliorates glucose extraction. By immunoprecipitation, GRK2 binds IRS1 but not the Ins receptor in an Ins-dependent fashion, which is lost in HEK-GRK2 cells. Ant-124 improves Ins-induced glucose uptake in HEK-293 and HEK-GRK2 cells, but does not prevent GRK2/IRS1 interaction. In SHR, Ant-124 infusion for 30 days ameliorates IRES and IRS1 tyrosine phosphorylation. CONCLUSION:Our results suggest that GRK2 mediates adrenergic IRES and that inhibition of GRK2 activity leads to increased Ins sensitivity both in cells and in animal model of IRES.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Cipolletta E,Campanile A,Santulli G,Sanzari E,Leosco D,Campiglia P,Trimarco B,Iaccarino Gdoi
10.1093/cvr/cvp252subject
Has Abstractpub_date
2009-12-01 00:00:00pages
407-15issue
3eissn
0008-6363issn
1755-3245pii
cvp252journal_volume
84pub_type
杂志文章abstract::Mayer waves are oscillations of arterial pressure occurring spontaneously in conscious subjects at a frequency lower than respiration (approximately 0.1 Hz in humans). Mayer waves are tightly coupled with synchronous oscillations of efferent sympathetic nervous activity and are almost invariably enhanced during states...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2005.11.008
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVE:Lower limb perfusion following arterial occlusion depends on the recruitment of collateral vessels. Blood flow through these collateral vessels may be jeopardized by hypersensitivity to vasoconstriction by serotonin (5-HT), as has been reported during hyperlipidemia and diabetes. Therefore the aim of this stu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00538-2
更新日期:2002-11-01 00:00:00
abstract::Segments of saphenous vein from patients undergoing coronary artery by-pass graft surgery were frozen in liquid nitrogen immediately on dissection (control), after stripping of the adventitia and side branch ligation (manipulation), after distention with blood (distention), or at completion of the last proximal anasto...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.6.326
更新日期:1985-06-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to quantify the changes in placental blood flow and combined ventricular output with gestational age in normal human fetuses to determine the percentage of total cardiac output that placental blood flow represented, and whether this changed with age. DESIGN:Two dimensional echocardiographic...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.7.603
更新日期:1991-07-01 00:00:00
abstract:AIMS:A blood pressure-independent metabolic shift toward a catabolic state upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. We sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa205
更新日期:2020-07-16 00:00:00
abstract:AIMS:The goal of this study was to determine whether the A1 adenosine receptor (AR) plays a role in atherosclerosis development and to explore its potential mechanisms. METHODS AND RESULTS:Double knockout (DKO) mice, deficient in the genes encoding A1 AR and apolipoprotein E (apoE), demonstrated reduced atheroscleroti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu033
更新日期:2014-04-01 00:00:00
abstract:OBJECTIVE:Macrophage migration inhibitory factor (MIF), which plays a pivotal role in the control of inflammatory responses, was first characterized as a T-cell cytokine, but later was also found as a pituitary peptide released in response to infection and stress. However, MIF's role and expression in the myocardium ha...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00408-4
更新日期:2001-12-01 00:00:00
abstract:OBJECTIVE:Ghrelin, the endogenous ligand of growth hormone secretagogue receptor (GHS-R), acts on the pituitary and the hypothalamus to stimulate the release of growth hormone (GH) and promotes appetite and adiposity. It has also been reported to increase myocardial contractility, induce vasodilation, and protect again...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.01.024
更新日期:2004-06-01 00:00:00
abstract::Cardiomyocyte death secondary to transient ischaemia occurs mainly during the first minutes of reperfusion in the form of contraction band necrosis. Research on the mechanisms leading to sarcolemmal rupture and necrosis during initial reperfusion identified several promising pharmacological targets directed either to ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvp109
更新日期:2009-07-15 00:00:00
abstract:OBJECTIVE:Cholinergic vasodilation has been thought to play little if any role in the regulation of blood pressure in humans. Autonomic denervation potentiates the vasoconstriction evoked by nitric oxide synthase inhibition in humans, but the mechanism is unclear. We hypothesized that this may be related to loss of neu...
journal_title:Cardiovascular research
pub_type: 临床试验,杂志文章
doi:10.1016/s0008-6363(01)00325-x
更新日期:2001-09-01 00:00:00
abstract:OBJECTIVE:The aim was to estimate the relative contributions of the various intracellular and sarcolemmal systems to the relaxation of the systolic calcium transient. METHODS:The experiments were performed on isolated rat ventricular myocytes. The cells were loaded with the fluorescent indicator indo-1 in order to mea...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.10.1826
更新日期:1993-10-01 00:00:00
abstract::Muscle tissue in atrioventricular (A-V) cardiac valve leaflets was studied in 35 human hearts and was found to be more prominent in the anterior leaflet of the mitral (MAL) than in the other valve leaflets. From serial sectioning and wax model reconstruction, the anatomic arrangement of the muscle in the MAL indicates...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/12.11.675
更新日期:1978-11-01 00:00:00
abstract:OBJECTIVE:Matrix metalloproteinase-9 (MMP-9) activity is up regulated in the heart subjected to ischemic insult. Whether increased MMP-9 activity contributes to acute myocardial injury after ischemia-reperfusion remains unknown. To investigate the role of MMP-9 in myocardial infarction, we utilized a MMP-9 knockout mou...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00254-7
更新日期:2002-06-01 00:00:00
abstract:Aims:Sirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in m...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy036
更新日期:2018-07-01 00:00:00
abstract:OBJECTIVE:The present study investigated whether activation of phosphatidylinositol 3-kinase (PI3-kinase) is involved in the stimulation of hypertrophic growth of adult ventricular cardiomyocytes under alpha- or beta-adrenoceptor stimulation. METHODS:Adult ventricular rat cardiomyocytes were used either directly after...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00171-0
更新日期:1998-10-01 00:00:00
abstract:AIMS:The discovery of a specific prorenin receptor (PRR) suggests a biological function of prorenin that is independent of angiotensin I production. In the present study, we investigated the role of PRR on smooth muscle cell (SMC) migration. METHODS AND RESULTS:PRR was expressed in human mammary arteries and in cultur...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs204
更新日期:2012-08-01 00:00:00
abstract::Hydrogen sulfide (H2S), as a gaseous signalling molecule, has been found to play important roles in postconditioning (PostC)-induced cardioprotection. Similar to nitric oxide (NO)-mediated protein S-nitrosylation (SNO), recent studies suggest that H2S could regulate protein function through another redox-based post-tr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw037
更新日期:2016-05-01 00:00:00
abstract:AIMS:Vascular inflammation is a major atherogenic factor and Toll-like receptor (TLR) 2 ligands, including bacterial and serum lipoproteins, seem to be involved in atherogenesis. On this basis, we analysed the effect of lipoproteins and different lipid components on TLR2-dependent signalling. METHODS AND RESULTS:In TL...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn087
更新日期:2008-08-01 00:00:00
abstract::Peptidyl-prolyl cis-trans-isomerases are a highly conserved family of immunophilins. The three peptidyl-prolyl cis-trans-isomerase subfamilies are cyclophilins, FK-506-binding proteins, and parvulins. Peptidyl-prolyl cis-trans-isomerases are expressed in multiple human tissues and regulate different cellular functions...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvv096
更新日期:2015-06-01 00:00:00
abstract:AIMS:Placental growth factor (PlGF), a homologue of vascular endothelial growth factor, is a pleiotropic cytokine with a pro-inflammatory activity. Previous gene-inactivation studies revealed that the loss of PlGF delays atherosclerotic lesion development and inhibits macrophage infiltration, but the activity of an ant...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp380
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVE:Both superoxide dismutase (SOD) and nitric oxide synthase (NOS) have been implicated in delayed preconditioning (DP) to ischemia/reperfusion (I/R) in the heart. We used isolated cardiac myocytes to test the hypothesis that SOD and NOS may interact in the development of DP. METHODS:Mouse neonatal cardiac myoc...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00502-9
更新日期:2003-10-01 00:00:00
abstract:OBJECTIVE:To determine the role of calcineurin and Src tyrosine kinase in the regulation of inducible nitric oxide synthase (iNOS) expression and protection in cardiomyocytes. METHODS:iNOS expression was studied in isolated neonatal rat ventricular myocyte cultures in response to bacterial lipopolysaccharide (LPS) or ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.05.026
更新日期:2006-09-01 00:00:00
abstract:OBJECTIVES:It has been shown that circulating human non-adherent CD34+ cells coexpressing vascular endothelial growth factor (VEGF)-R2 and AC133 have the capacity to differentiate into adherent mature endothelial cells. However, prior studies have demonstrated that a much bigger subset of primary adherent mononuclear c...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00270-4
更新日期:2001-02-16 00:00:00
abstract:OBJECTIVE:To examine whether altered PCO2 or HCO3- at normal pH potentiate agonist-induced vasoconstriction of small pulmonary arteries, and if so to determine the mechanism. METHODS:Small intrapulmonary arteries (IPA) from rats were mounted on a myograph and PGF2alpha (3 microM)-induced tension recorded before and 40...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.10.038
更新日期:2005-02-01 00:00:00
abstract:OBJECTIVE:We recently demonstrated in our swine model of coronary artery spasm that enhanced myosin light chain (MLC) phosphorylations (both MLC mono- and diphosphorylations) play a central role in the pathogenesis of the spasm. However, the molecular mechanism for and the phosphorylation sites for the enhanced MLC pho...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00144-3
更新日期:1999-09-01 00:00:00
abstract:AIMS:in this study, we attempted to detect a recent myocardial ischaemic event using ultrasound molecular imaging (UMI) with microbubbles (MB) targeted to intercellular adhesion molecule-1 (ICAM-1) in the late phase of reperfusion. METHODS AND RESULTS:we created a myocardial ischaemia-reperfusion model in 60 C57/BL ma...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq269
更新日期:2011-01-01 00:00:00
abstract:STUDY OBJECTIVE:The aim of the study was to examine, in a whole heart preparation, the relationship between length changes in cardiac muscle and tension development and length dependent activation. DESIGN:Rat hearts were perfused by the Langendorff technique and isovolumetric pressure changes in the left ventricle, pr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.3.254
更新日期:1990-03-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to compare the temporal sequence and structural relationship between perivascular and interstitial fibrosis and microscopic scarring seen in the left ventricle in response to either a transient or sustained stimulus to fibrosis. DESIGN:In 72 male Wistar rats (250-350 g) the transient stimul...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.9.741
更新日期:1990-09-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to evaluate the influence that centrally administered angiotensin-II has on the intrarenal renin-angiotensin system and renal sympathetic nerve activity. DESIGN:Renal responses to centrally administered angiotensin-II (10 micrograms) or saralasin (50 micrograms) were measured in anaesthetis...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.5.353
更新日期:1991-05-01 00:00:00
abstract:OBJECTIVES:Recombinant retroviral vectors have been shown to be useful tools for marking cells so as to follow their fates during development. The aim of this study was to determine the utility and advantages of an adenoviral vector as a tool to study the heart as it develops from a simple tube into a complex four-cham...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00