Abstract:
RATIONALE:Elevations in C-reactive protein (CRP) are associated with increased cardiovascular disease risk and endothelial dysfunction. CRP antagonizes endothelial nitric oxide synthase (eNOS) through processes mediated by the IgG receptor Fcγ receptor IIB (FcγRIIB), its immunoreceptor tyrosine-based inhibitory motif, and SH2 domain-containing inositol 5'-phosphatase 1. In mice, CRP actions on eNOS blunt carotid artery re-endothelialization. OBJECTIVE:How CRP activates FcγRIIB in endothelium is not known. We determined the role of Fcγ receptor I (FcγRI) and the basis for coupling of FcγRI to FcγRIIB in endothelium. METHODS AND RESULTS:In cultured endothelial cells, FcγRI-blocking antibodies prevented CRP antagonism of eNOS, and CRP activated Src via FcγRI. CRP-induced increases in FcγRIIB immunoreceptor tyrosine-based inhibitory motif phosphorylation and SH2 domain-containing inositol 5'-phosphatase 1 activation were Src-dependent, and Src inhibition prevented eNOS antagonism by CRP. Similar processes mediated eNOS antagonism by aggregated IgG used to mimic immune complex. Carotid artery re-endothelialization was evaluated in offspring from crosses of CRP transgenic mice (TG-CRP) with either mice lacking the γ subunit of FcγRI (FcRγ(-/-)) or FcγRIIB(-/-) mice. Whereas re-endothelialization was impaired in TG-CRP vs wild-type, it was normal in both FcRγ(-/-); TG-CRP and FcγRIIB(-/-); TG-CRP mice. CONCLUSIONS:CRP antagonism of eNOS is mediated by the coupling of FcγRI to FcγRIIB by Src kinase and resulting activation of SH2 domain-containing inositol 5'-phosphatase 1, and consistent with this mechanism, both FcγRI and FcγRIIB are required for CRP to blunt endothelial repair in vivo. Similar mechanisms underlie eNOS antagonism by immune complex. FcγRI and FcγRIIB may be novel therapeutic targets for preventing endothelial dysfunction in inflammatory or immune complex-mediated conditions.
journal_name
Circ Resjournal_title
Circulation researchauthors
Sundgren NC,Zhu W,Yuhanna IS,Chambliss KL,Ahmed M,Tanigaki K,Umetani M,Mineo C,Shaul PWdoi
10.1161/CIRCRESAHA.111.254573subject
Has Abstractpub_date
2011-10-28 00:00:00pages
1132-40issue
10eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.111.254573journal_volume
109pub_type
杂志文章abstract:RATIONALE:Calcium channel blockers (CCBs) are an important class of drugs in managing cardiovascular diseases. Patients usually rely on these medications for the remainder of their lives after diagnosis. Although the acute pharmacological actions of CCBs in the hearts are well-defined, little is known about the drug-sp...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.314202
更新日期:2019-07-05 00:00:00
abstract::Complete knowledge of myocardial structure, metabolism, and function is crucial to understanding the response of the heart to injury such as ischemia. Increasingly, this type of knowledge is required at multiple levels, from that of the isolated myocyte to the functioning organism, to provide basic scientists and clin...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000103863.40055.E8
更新日期:2003-12-12 00:00:00
abstract::To determine whether the attenuation in the growth capacity of myocytes in the overloaded aging heart is associated with an impairment in the activation of insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) in the stressed cells, large myocardial infarcts were produced in Fischer 344 rats at 4 and 16 month...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.4.536
更新日期:1996-04-01 00:00:00
abstract::Shear stress caused by the frictional forces of a fluid moving over a cell monolayer is an important regulator of gene expression. In this study, we investigated the effect of shear stress on angiotensin-converting enzyme (ACE) expression and promoter activity in vitro and on local vascular ACE activity in vivo. ACE a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.3.312
更新日期:1997-03-01 00:00:00
abstract::Our goal in this review is to discuss the pathophysiology, diagnosis, and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms intracranial stenosis and int...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.308441
更新日期:2017-02-03 00:00:00
abstract::Age-related diastolic dysfunction is a major factor in the epidemic of heart failure. In patients hospitalized with heart failure, HFpEF is now as common as heart failure with reduced ejection fraction. We now have many successful treatments for heart failure with reduced ejection fraction, while specific treatment op...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.115.302929
更新日期:2014-06-20 00:00:00
abstract::High sodium intake (HNa) increases brain ouabainlike activity (OLA) in rats. In spontaneously hypertensive rats (SHR), HNa exaggerates development of hypertension and pressor and sympathoexcitatory responses to stress. To investigate whether dietary sodium-induced changes in brain OLA play a functional role, responses...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.2.430
更新日期:1992-02-01 00:00:00
abstract:RATIONALE:Depletion of medial smooth muscle cell (SMC) is a major pathological characteristic of abdominal aortic aneurysm (AAA), although the mechanism by which these cells are eliminated remains incompletely understood. We reasoned that necroptosis, a recently described form of necrosis mediated by receptor-interacti...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.304899
更新日期:2015-02-13 00:00:00
abstract::The extracellular pH (pHo) and intracellular pH (pHi) were simultaneously measured with H(+)-sensitive microelectrodes in the rabbit papillary muscle during normal arterial perfusion and no-flow ischemia. The preparation was kept in an artificial gaseous atmosphere (N2 and CO2 during ischemia) without a surrounding fl...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.2.460
更新日期:1992-08-01 00:00:00
abstract::The cardiac high molecular weight proteins/ryanodine receptors were purified to homogeneity from junctional sarcoplasmic reticulum membranes and shown to exhibit large conductance calcium channel activity. High molecular weight proteins were solubilized from junctional sarcoplasmic reticulum in zwitterionic detergent ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.4.779
更新日期:1989-04-01 00:00:00
abstract::Volume expansion has been shown to increase plasma atrial natriuretic peptide (ANP) levels, but the precise role of paracrine and autocrine factors in stretch-induced cardiac hormone release is not clear. In the present study, we report the effects of endothelin (ET) and angiotensin receptor (AT receptor) antagonists ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.1.114
更新日期:1997-01-01 00:00:00
abstract:RATIONALE:Plasminogen activator inhibitor-1 (PAI-1) is a biomarker for several vascular disease states; however, its target of action within the vessel wall is undefined. OBJECTIVE:Determine the ability of PAI-1 to regulate myoendothelial junction (MEJ) formation. METHODS AND RESULTS:MEJs are found throughout the vas...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.215723
更新日期:2010-04-02 00:00:00
abstract::The solid angle theory has long been applied to the interpretation of the ECG; however, quantitative evaluation of its applicability has been minimal. We applied solid angle analysis to the interpretation of the TQ-ST deflection during acute ischemia. Five anesthetized pigs were studied 1--3 hours after coronary occlu...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.43.6.879
更新日期:1978-12-01 00:00:00
abstract::To determine whether calcium channel agonists and antagonists bind to distinct pharmacologically active sites, the binding of dihydropyridine calcium channel agonists and antagonists was related to calcium flux and contractile state in primary monolayer cultures of spontaneously contracting chick embryo ventricular ce...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.5.683
更新日期:1987-05-01 00:00:00
abstract::Magnesium modulates vascular smooth muscle cell (VSMC) function. However, molecular mechanisms regulating VSMC Mg2+ remain unknown. Using biochemical, pharmacological, and genetic tools, the role of transient receptor potential membrane melastatin 7 (TRPM7) cation channel in VSMC Mg2+ homeostasis was evaluated. Rat, m...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000152967.88472.3e
更新日期:2005-02-04 00:00:00
abstract::The possibility of an interaction between the cytoskeletal protein dystrophin and cell surface caveolae in the mammalian myocardium was investigated by several techniques. Caveolin (cav)-3-enriched, detergent-insoluble membranes isolated from purified ventricular sarcolemma by density-gradient fractionation were found...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.6.480
更新日期:2000-09-15 00:00:00
abstract::We studied the effects of slow continuous hemorrhage (0.5 ml/kg per min) on measurements of arterial and left atrial pressures, and renal nerve activity in conscious dogs with all reflexes intact, or after sinoaortic baroreceptor denervation, cardiac denervation, or sinoaortic baroreceptor denervation plus vagal dener...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.5.788
更新日期:1985-11-01 00:00:00
abstract::RhoA and Rac1 regulate formation of stress fibers and intercellular junctions, thus modulating endothelial monolayer permeability. Posttranslational modifications of RhoA and Rac1 regulate enzyme activity and subcellular localization, resulting in altered cellular function. The role of RhoA and Rac1 carboxyl methylati...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000113923.85084.C1
更新日期:2004-02-20 00:00:00
abstract::We used plethysmograph techniques to measure or calculate the tissue and capillary forces and flows (capillary pressure, tissue and plasma oncotic pressure, transcapillary pressure drop, lymph flow, and interstitial pressure) in a dog hindpaw preparation in situ at three different venous pressures (PV). Since lymph wa...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.2.245
更新日期:1976-08-01 00:00:00
abstract:RATIONALE:Voltage-gated sodium channels initiate action potentials in excitable tissues. Mice in which Scn5A (the predominant sodium channel gene in heart) has been knocked out die early in development with cardiac malformations by mechanisms which have yet to be determined. OBJECTIVE:Here we addressed this question b...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.213132
更新日期:2010-04-30 00:00:00
abstract::The microelectrode technique of intracellular constant current application and intracellular transmembrane voltage recording was used to study the effects of procaine amide (PA) on cardiac excitability. We measured the effect of PA in a concentration equivalent to clinically effective antiarrhythmic plasma levels (5 m...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.38.2.115
更新日期:1976-02-01 00:00:00
abstract::We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs-Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Con...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.3.881
更新日期:1991-09-01 00:00:00
abstract::In studies that attempt to measure intracellular calcium [( Ca2+]i) in the intact heart with the calcium indicator indo 1-AM, a fundamental assumption is that the signals report changes in myocyte [Ca2+]i. We studied isolated perfused rabbit hearts loaded with the calcium probe indo 1-AM and recorded surface fluoresce...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.2.415
更新日期:1990-08-01 00:00:00
abstract::The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the le...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.1.63
更新日期:1989-07-01 00:00:00
abstract::This paper describes use of the Karhunen-Loeve expansion to identify and reduce temporal redundancy in electrocardiographic body surface potential maps (192 body surface leads recorded simultaneously at 1 kHz/channel for approximately 600 msec). Temporal data compression of about 20 to 1 was obtained with accurate rep...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.49.1.197
更新日期:1981-07-01 00:00:00
abstract::Mast cells in rat hearts were studied quantitatively during normal postnatal growth and in two types of cardiac hypertrophy. Normally, cardiac mast cell density in 11-12-day-old animals is very low, but increases markedly in the following 2-3 weeks to its highest values, with a subsequent decline toward adult values. ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.2.511
更新日期:1990-02-01 00:00:00
abstract::The structure of the mouse natriuretic peptide type-B (BNP) gene was determined by isolating and sequencing genomic clones. The mouse BNP gene was structurally similar to other natriuretic peptide genes and comprised three exons and two introns. Expression of the mouse BNP gene was found only in cardiac tissue as dete...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.5.984
更新日期:1993-05-01 00:00:00
abstract::The cardioprotection by ischemic preconditioning is lost in aged wild-type and in STAT3 (signal transducer and activator of transcription 3)-deficient mice. The aim of the present study was to analyze whether or not ischemic postconditioning (iPoco) was effective in aged mice hearts and whether iPoco was dependent on ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.164699
更新日期:2008-01-04 00:00:00
abstract::The inward current ("oscillatory current") which may be present after the end of a depolarizing clamp was studied in sheep cardiac Purkinje fibers by means of a voltage-clamp method. The following results were obtained. In order to appear, the oscillatory current (Ios) requires a previous depolarization to approximate...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.48.5.618
更新日期:1981-05-01 00:00:00
abstract::We have previously demonstrated that urokinase-type plasminogen activator (uPA) is highly expressed in the aneurysmal segment of the abdominal aorta (AAA) in apolipoprotein E-deficient (apoE-/-) mice treated with angiotensin II (Ang II). In the present study, we tested the hypothesis that uPA is essential for AAA form...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000061571.49375.E1
更新日期:2003-03-21 00:00:00