Abstract:
BACKGROUND:Adenylyl cyclases (ACs) are a family of effector molecules for G-protein-coupled receptors. The 2 ACs most abundantly expressed in cardiac myocytes are types 5 (AC5) and 6 (AC6), which have 65% amino acid homology. It has been speculated that coexpression of 2 AC types in cardiac myocytes represents redundancy, but the specific role of AC6 in cardiac physiology and its differences from AC5 remain to be defined. METHODS AND RESULTS:We generated transgenic mice with targeted deletion of AC6. Deletion of AC6 was associated with reduced left ventricular contractile function (P=0.026) and relaxation (P=0.041). The absence of AC6 was associated with a 48% decay in beta-adrenergic receptor-stimulated cAMP production in cardiac myocytes (P=0.003) and reduced protein kinase A activity (P=0.015). In addition, phospholamban phosphorylation was reduced (P=0.015), sarcoplasmic reticulum Ca2+-ATPase activity was impaired (P<0.0001), and cardiac myocytes showed marked abnormalities in calcium transient formation (P=0.001). CONCLUSIONS:The combination of impaired cardiac cAMP generation and calcium handling that result from AC6 deletion underlies abnormalities in left ventricular function. The biochemical and physiological consequences of AC6 deletion reveal it to be an important effector molecule in the adult heart, serving unique biological functions not replicated by AC5.
journal_name
Circulationjournal_title
Circulationauthors
Tang T,Gao MH,Lai NC,Firth AL,Takahashi T,Guo T,Yuan JX,Roth DM,Hammond HKdoi
10.1161/CIRCULATIONAHA.107.730069subject
Has Abstractpub_date
2008-01-01 00:00:00pages
61-9issue
1eissn
0009-7322issn
1524-4539pii
CIRCULATIONAHA.107.730069journal_volume
117pub_type
杂志文章相关文献
CIRCULATION文献大全abstract:BACKGROUND:Angiotensin-converting enzyme (ACE) inhibition potentiates the tissue-type plasminogen activator (t-PA) response to exogenous bradykinin. This study tested the hypothesis that ACE inhibition increases endothelial t-PA release through endogenous bradykinin. METHODS AND RESULTS:We measured the effect of intra...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.0000046268.59922.a4
更新日期:2003-02-04 00:00:00
abstract:BACKGROUND:Arteriogenesis serves as an efficient mechanism for flow restoration after arterial occlusion. This process is associated with inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), although their role in arteriogenesis remains unclear. We hypothesized that arteriogenesis is reduced in mice ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.0000014987.32865.8e
更新日期:2002-04-09 00:00:00
abstract:BACKGROUND:Hypertension and other vascular diseases are more prevalent in diabetic patients than in the general population. In humans and in several animal models of diabetes, a disturbance of endothelium-dependent responses has been shown. Oxyhemoglobin is one of the most known modulators of these endothelium-dependen...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.88.5.2111
更新日期:1993-11-01 00:00:00
abstract:BACKGROUND:Because pulmonary artery size is considered by most investigators to be a major prognosticator of outcome in patients undergoing staged Fontan reconstruction, the objective of the present study was to determine the efficacy of noninvasive measures in determining pulmonary artery size. METHODS AND RESULTS:Th...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.90.6.2927
更新日期:1994-12-01 00:00:00
abstract:BACKGROUND:Protease-activated receptor-1 (PAR-1) is the high-affinity receptor for the coagulation protease thrombin. It is expressed by a variety of cell types in the heart, including cardiomyocytes and cardiac fibroblasts. We have shown that tissue factor (TF) and thrombin contribute to infarct size after cardiac isc...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.107.692764
更新日期:2007-11-13 00:00:00
abstract:BACKGROUND:Autograft reinforcement interventions (R) during the Ross procedure are intended to preserve autograft function and improve durability. The aim of this study is to evaluate this hypothesis. METHODS AND RESULTS:1335 adult patients (mean age:43.5+/-12.0 years) underwent a Ross procedure (subcoronary, SC, n=63...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.843391
更新日期:2009-09-15 00:00:00
abstract::Certain clinical and morphologic observations are described in 27 patients with severe isolated angina pectoris of either the stable (five patients) or the unstable form (22 patients). Twenty-four patients died during or shortly after cardiac operations designed to relieve angina pectoris and three died during cardiac...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.54.3.388
更新日期:1976-09-01 00:00:00
abstract:BACKGROUND:Monocyte chemoattractant protein-1 (MCP-1) is a chemokine responsible for the recruitment of monocytes to sites of inflammation. MCP-1 appears to play a critical role at multiple stages in atherosclerosis, including the initiation of the fatty streak, promotion of plaque instability, and remodeling after myo...
journal_title:Circulation
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1161/01.cir.0000049742.68848.99
更新日期:2003-02-11 00:00:00
abstract:BACKGROUND:The mechanisms responsible for tumor necrosis factor (TNF)-induced LV structural remodeling in the adult heart are not known. METHODS AND RESULTS:We generated a line of transgenic mice (MHCsTNF) with cardiac restricted overexpression of TNF that develop progressive LV dilation/remodeling from 4 to 12 weeks ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/hc3401.093154
更新日期:2001-08-14 00:00:00
abstract:BACKGROUND:Central aortic pressures and waveform convey important information about cardiovascular status, but direct measurements are invasive. Peripheral pressures can be measured noninvasively, and although they often differ substantially from central pressures, they may be mathematically transformed to approximate ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.95.7.1827
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND:Inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H) exhibit marked differences in atherosclerosis susceptibility. We sought to determine whether the difference in atherosclerosis susceptibility resides at the level of arterial walls. METHODS AND RESULTS:Thoracic aortic segments from 8-week-old female B6 an...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.106.640185
更新日期:2006-11-28 00:00:00
abstract::Although the postoperative hemodynamic and echocardiographic features of idiopathic hypertrophic subaortic stenosis have been studied, the expected consistent postoperative thinning of the interventricular septum has not been reported. In this study, the short-term effects of septal myectomy were evaluated in 16 patie...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.58.5.850
更新日期:1978-11-01 00:00:00
abstract::Labetalol was administered to six hypertensive subjects in increasing doses for seven days. A decrease in both supine and standing arterial pressure and heart rate was observed with no change in cardiac output and few side effects. Exercise tolerance was unaltered by the drug, but the heart rate and arterial pressure ...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/01.cir.55.2.370
更新日期:1977-02-01 00:00:00
abstract:BACKGROUND:Angiogenic placental growth factor (PlGF) concentrations rise during pregnancy, peaking at the end of midpregnancy. Low PlGF concentrations during pregnancy are associated with pregnancy complications with recognized later-life cardiovascular risk. We hypothesized that low PlGF concentrations, especially in ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.118.036632
更新日期:2019-04-02 00:00:00
abstract::Although exercise ECG testing has been shown to have important prognostic value after acute myocardial infarction, exercise 201Tl scintigraphy offers several potential advantages, including: 1) increased sensitivity for detecting residual myocardial ischemia; 2) the ability to localize ischemia to a specific area or a...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract::This study explored the association between sodium excretion and blood pressure (BP). A new method was used to minimize the measurement error introduced by the large intrinsic variability of 24-hour sodium excretion. The ratio of intra- to interindividual variation was used to estimate the number of measurements neede...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.62.1.97
更新日期:1980-07-01 00:00:00
abstract:BACKGROUND:Oxidized LDL (oxLDL) is thought to play a key role in the inflammatory response in the arterial vessel wall. METHODS AND RESULTS:In a prospective, nested, case-control study, the association between plasma oxLDL and risk of an acute coronary heart disease (CHD) event was investigated in men without prevalen...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.104.529297
更新日期:2005-08-02 00:00:00
abstract:BACKGROUND:Vasodilatory shock is a potentially lethal complication of severe disease in critically ill patients. Currently, catecholamines are the most widely used vasopressor agents to support blood pressure, but loss of catecholamine pressor effects is a well-known clinical dilemma. Arginine vasopressin (AVP) has rec...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.CIR.0000066692.71008.BB
更新日期:2003-05-13 00:00:00
abstract:BACKGROUND:In people with atrial fibrillation (AF), periods of sinus rhythm present an opportunity to detect prothrombotic atrial remodeling through measurement of P-wave indices (PWIs)-prolonged P-wave duration, abnormal P-wave axis, advanced interatrial block, and abnormal P-wave terminal force in lead V1. We hypothe...
journal_title:Circulation
pub_type: 杂志文章,多中心研究
doi:10.1161/CIRCULATIONAHA.118.035411
更新日期:2019-01-08 00:00:00
abstract::Trapidil (triazolopyrimidine) possesses activity against platelet-derived growth factor-induced cellular proliferation in vitro and intimal proliferation in vivo. The objective of this study was to determine if trapidil could prevent restenosis in experimentally induced atherosclerotic rabbits. New Zealand White rabbi...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.81.3.1089
更新日期:1990-03-01 00:00:00
abstract:BACKGROUND:Low-density lipoprotein (LDL) impairs endothelial cell function by uncoupling endothelial nitric oxide synthase (eNOS) activity, which allows superoxide anion (O2*-)) to be generated rather than nitric oxide (*NO). Recent reports indicate that apolipoprotein (apo) A-1 mimetics inhibit the development of athe...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.0000061949.17174.b6
更新日期:2003-03-25 00:00:00
abstract:BACKGROUND:The endocrine-disrupting chemical bisphenol A (BPA) is widely used in food and beverage packaging. Higher urinary BPA concentrations were cross-sectionally associated with heart disease in National Health and Nutrition Examination Survey (NHANES) 2003-2004 and NHANES 2005-2006, independent of traditional ris...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.111.069153
更新日期:2012-03-27 00:00:00
abstract:BACKGROUND:Ischemic preconditioning attenuates the effects of subsequent sustained ischemia by a mechanism involving adenosine and G proteins in several species. Adenosine is not involved in ischemic preconditioning of rat hearts, the mechanisms of which are poorly understood. METHODS AND RESULTS:Reduction of isometri...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.92.8.2259
更新日期:1995-10-15 00:00:00
abstract::The elimination of specific dietary cholesterol target recommendations in recent guidelines has raised questions about its role with respect to cardiovascular disease. This advisory was developed after a review of human studies on the relationship of dietary cholesterol with blood lipids, lipoproteins, and cardiovascu...
journal_title:Circulation
pub_type: 杂志文章,meta分析
doi:10.1161/CIR.0000000000000743
更新日期:2020-01-21 00:00:00
abstract:BACKGROUND:Early graft failure after the use of less satisfactory autologous grafts (30% of all vein grafts) is caused primarily by the following problems: (1) suitable autologous transplants are limited; (2) biotechnology has not yet been able to produce reliable graft substitutes that are legally and ethically approv...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:
更新日期:2001-09-18 00:00:00
abstract:BACKGROUND:The pathophysiological mechanisms leading to acceleration of ventricular tachycardia (VT) are still unclear. METHODS AND RESULTS:High-resolution epicardial mapping was used to study the mechanisms of VT acceleration by programmed electrical stimulation (PES) in a model of sustained reentrant VT in Langendor...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.83.5.1621
更新日期:1991-05-01 00:00:00
abstract:BACKGROUND:Mutations in sarcomere protein, PRKAG2, LAMP2, alpha-galactosidase A (GLA), and several mitochondrial genes can cause rare familial cardiomyopathies, but their contribution to increased left ventricular wall thickness (LVWT) in the community is unknown. METHODS AND RESULTS:We studied 1862 unrelated particip...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.593558
更新日期:2006-06-13 00:00:00
abstract::To study the variability of the fraction of CPK released from the infarcted heart which enters the serum (serum entry ratio, or SER) with size and model of infarction, nine dogs underwent homogeneous infarctions (LAD ligation) of varying sizes, and 10 dogs underwent scattered infarctions (left coronary embolization). ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.58.6.1143
更新日期:1978-12-01 00:00:00
abstract:BACKGROUND:Endurance athletes have higher high density lipoprotein (HDL) concentrations than sedentary controls. To examine the mechanism for this effect, we compared HDL apoprotein metabolism in 10 endurance athletes aged 34 +/- 6 years (mean +/- SD) and 10 sedentary men aged 36 +/- 8 years. METHODS AND RESULTS:Subje...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.84.1.140
更新日期:1991-07-01 00:00:00
abstract:BACKGROUND:Among patients with documented stable coronary artery disease and in whom no revascularization was performed, we compared the respective values of angiographic diameter stenosis (DS) and fractional flow reserve (FFR) in predicting natural history. METHODS:The present analysis included the 607 patients from ...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCULATIONAHA.117.028782
更新日期:2018-04-03 00:00:00