Abstract:
BACKGROUND:AMP-activated protein kinase (AMPK) is a stress-activated protein kinase that works as a metabolic sensor of cellular ATP levels. Here, we investigated whether AMPK signaling has a role in the regulation of the angiotensin II (Ang II)-induced proliferation signal in rat vascular smooth muscle cells (VSMCs). METHODS AND RESULTS:Aminoimidazole-4-carboxamide-1-beta-ribofuranoside (AICAR) activated AMPK in rat VSMCs and inhibited Ang II-induced extracellular signal-regulated kinase 1/2 phosphorylation but not that of p38 MAPK or Akt/PKB. Although Ang II activated AMPK, this activation was significantly inhibited by catalase, N-acetylcysteine, and diphenyleneiodonium chloride, an NADPH oxidase inhibitor. Moreover, the observation that AMPK was activated by H2O2 suggests that AMPK is redox sensitive. The Ang II type 1 receptor antagonist valsartan but not the Ang II type 2 receptor antagonist PD123319 significantly inhibited Ang II-induced AMPK activation, suggesting that Ang II-induced AMPK activation was Ang II type 1 receptor dependent. Whereas 3H-thymidine incorporation by VSMCs treated with Ang II was significantly inhibited when the cells were pretreated with 1 mmol/L AICAR, the inhibition of AMPK by dominant-negative AMPK overexpression augmented Ang II-induced cell proliferation. Subcutaneous injection of AICAR (1 mg/g body weight per day) for 2 weeks suppressed neointimal formation after transluminal mechanical injury of the rat femoral artery. CONCLUSIONS:Our findings indicate that Ang II-induced AMPK activation is synchronized with extracellular signal-regulated kinase signaling and that AMPK works as an inhibitor of the Ang II proliferative pathway. AMPK signaling might serve as a new therapeutic target of vascular remodeling in cardiovascular diseases.
journal_name
Circulationjournal_title
Circulationauthors
Nagata D,Takeda R,Sata M,Satonaka H,Suzuki E,Nagano T,Hirata Ydoi
10.1161/01.CIR.0000136025.96811.76subject
Has Abstractpub_date
2004-07-27 00:00:00pages
444-51issue
4eissn
0009-7322issn
1524-4539pii
01.CIR.0000136025.96811.76journal_volume
110pub_type
杂志文章相关文献
CIRCULATION文献大全abstract::Cardiovascular disease continues to be the leading cause of death among women in the United States. One of the barriers to improving cardiovascular disease outcomes in women is the lack of reliable, effective screening modalities. Breast arterial calcification has emerged as a potential risk stratification tool. Local...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.118.038092
更新日期:2019-02-19 00:00:00
abstract:BACKGROUND:Pulmonary hypertension is a fatal disease characterized by vasoconstriction and vascular remodeling. Loss of endothelial nitric oxide bioavailability is implicated in pulmonary hypertension pathogenesis. Recent evidence suggests that the cofactor tetrahydrobiopterin (BH4) is an important regulator of nitric ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000162470.26840.89
更新日期:2005-04-26 00:00:00
abstract:BACKGROUND:After cardiopulmonary bypass (CPB), pulmonary hypertension and its associated increased vascular reactivity are a major source of morbidity, particularly for children with increased pulmonary blood flow. Although post-CPB pulmonary hypertension is well described, its mechanisms remain incompletely understood...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.95.4.1054
更新日期:1997-02-18 00:00:00
abstract::Over the last 20 years, operative mortality has decreased and late survival has improved for patients with chronic stable angina who have coronary artery bypass surgery. However, this favorable trend may not continue because the operation is now extended to elderly and high-risk patients. The most powerful predictors ...
journal_title:Circulation
pub_type: 临床试验,杂志文章,评审
doi:
更新日期:1989-06-01 00:00:00
abstract::Ventricular mural thrombi complicate many cardiac diseases. The endocardial endothelium can modulate the mechanical performance of subjacent myocardium and mediate responses to certain physiopharmacologic agents. We studied the effects of aggregating platelets on the contractile performance of isolated cardiac muscle....
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.79.6.1315
更新日期:1989-06-01 00:00:00
abstract:BACKGROUND:Tetralogy of Fallot is the most common form of congenital heart disease in implantable cardioverter-defibrillator (ICD) recipients, yet little is known about the value of ICDs in this patient population. METHODS AND RESULTS:We conducted a multicenter cohort study in high-risk patients with Tetralogy of Fall...
journal_title:Circulation
pub_type: 杂志文章,多中心研究
doi:10.1161/CIRCULATIONAHA.107.726372
更新日期:2008-01-22 00:00:00
abstract:BACKGROUND:Recombinant DNA technologies have facilitated the development of a set of polymorphic DNA markers covering the human genome. General linkage analysis in families predisposed to inherited disease is now feasible. Linkage analysis can help identify a disease gene even when relatively little is known about the ...
journal_title:Circulation
pub_type: 杂志文章,评审
doi:10.1161/01.cir.85.6.1973
更新日期:1992-06-01 00:00:00
abstract::Nine patients with severe mitral disease were studied before and six months after mitral valve replacement with a three-cusp stented prosthesis using fresh autologous fascia lata tissue. Only patients in whom there was no auscultatory and angiographic evidence of incompetence of the replaced valve were selected for re...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.52.5.880
更新日期:1975-11-01 00:00:00
abstract:BACKGROUND:Patients with diabetes mellitus (DM) are at high risk of developing congestive heart failure (CHF). However, the relationships between glucose levels and CHF in people with or without a history of DM have not been well characterized. METHODS AND RESULTS:We evaluated the associations between fasting plasma g...
journal_title:Circulation
pub_type: 杂志文章,随机对照试验
doi:10.1161/CIRCULATIONAHA.106.661405
更新日期:2007-03-20 00:00:00
abstract:BACKGROUND:Older coronary patients are at high risk of cardiac disability. Exercise conditioning programs have been demonstrated to improve functional capacity, particularly in younger coronary patients. In this study, the effects of aerobic conditioning on submaximal and maximal indicators of exercise performance were...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.88.2.572
更新日期:1993-08-01 00:00:00
abstract:BACKGROUND:A low level of HDL cholesterol has been identified as a risk factor for stroke in observational studies. METHODS AND RESULTS:Our objective was to determine whether treatment aimed at raising HDL cholesterol and lowering triglycerides reduces stroke in men with coronary heart disease and low levels of both H...
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.103.23.2828
更新日期:2001-06-12 00:00:00
abstract::An asymptomatic 14-year-old male was found at cardiac catheterization to have a coronary artery fistula involving a vessel originating from the left main coronary artery and terminating in the right heart. Chest X-ray and electrocardiogram were within normal limits and shunt flow was too small to be detected by oximet...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.57.1.197
更新日期:1978-01-01 00:00:00
abstract:BACKGROUND:With MRI, an index of myocardial perfusion reserve (MPRI) can be determined. We assessed the value of this technique for the noninvasive detection of coronary artery disease (CAD) in patients with suspected CAD. METHODS AND RESULTS:Eighty-four patients referred for a primary diagnostic coronary angiography ...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/01.CIR.0000080915.35024.A9
更新日期:2003-07-29 00:00:00
abstract:BACKGROUND:Recent studies have suggested that endogenous erythropoietin (Epo) plays an important role in the mobilization of bone marrow-derived endothelial progenitor cells (EPCs). However, it remains to be elucidated whether the Epo system exerts protective effects on pulmonary hypertension (PH), a fatal disorder enc...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.583732
更新日期:2006-03-21 00:00:00
abstract:BACKGROUND:In subjects of all ages, those who weigh the most often have the highest blood pressure. Thus, in epidemiological studies, weight is the most important correlate of blood pressure. Using the data from the Medical College of Virginia Twin Study, we asked these questions: 1) Do the same genetic paths that regu...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.86.6.1780
更新日期:1992-12-01 00:00:00
abstract:BACKGROUND:There is no treatment proven to limit the growth of abdominal aortic aneurysms, in which the histological hallmarks include inflammation and medial atrophy, with apoptosis of smooth muscle cells and destruction of elastin. METHODS AND RESULTS:Aneurysm biopsies were used for explant cultures, the preparation...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.100.1.48
更新日期:1999-07-06 00:00:00
abstract:BACKGROUND:Normal mammalian mitral leaflets have regional heterogeneity of biochemical composition, collagen fiber orientation, and geometric deformation. How leaflet shape and regional geometry are affected in dilated cardiomyopathy is unknown. METHODS AND RESULTS:Nine sheep had 8 radio-opaque markers affixed to the ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.000554
更新日期:2006-07-04 00:00:00
abstract:BACKGROUND:The recent breakthrough in the generation of induced pluripotent stem (iPS) cells, which are almost indistinguishable from embryonic stem (ES) cells, facilitates the generation of murine disease- and human patient-specific stem cell lines. The aim of this study was to characterize the cardiac differentiation...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.778795
更新日期:2008-07-29 00:00:00
abstract:BACKGROUND:The goal of this study was to assess the clinical value of stress myocardial perfusion scintigraphy (MPS) in elderly patients (> or =75 years of age). METHODS AND RESULTS:We followed up 5200 elderly patients (41% exercise) after dual-isotope MPS over 2.8+/-1.7 years (362 cardiac deaths [CDs], 7.0%, 2.6%/y) ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.817387
更新日期:2009-12-01 00:00:00
abstract:BACKGROUND:Lifetime risk for atherosclerotic cardiovascular disease (CVD) has not previously been estimated, and the effect of risk factor burden on lifetime risk is unknown. METHODS AND RESULTS:We included all Framingham Heart Study participants who were free of CVD (myocardial infarction, coronary insufficiency, ang...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.548206
更新日期:2006-02-14 00:00:00
abstract:BACKGROUND:A complete understanding of fluid mechanics in Fontan physiology includes knowledge of the caval contributions to right (RPA) and left (LPA) pulmonary arterial blood flow, total systemic venous return, and relative blood flow to each lung. METHODS AND RESULTS:Ten Fontan patients underwent cine MRI. Three ci...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.99.9.1215
更新日期:1999-03-09 00:00:00
abstract:BACKGROUND:Although lipoprotein(a) (Lp[a]) is a risk factor for atherosclerosis, no study has documented the effects of Lp(a) on angiogenesis. In this study, we examined collateral formation in peripheral arterial disease (PAD) model in Lp(a) transgenic mice. In addition, we examined the feasibility of gene therapy by ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.0000012146.07240.fd
更新日期:2002-03-26 00:00:00
abstract:BACKGROUND:For decades, the coronary heart disease (CHD) mortality rate has been four or more times higher in Finland than in France despite comparable intakes of dietary cholesterol and saturated fat. A potential answer to this paradox is provided by this study of 40 countries and the analyses of other nutrients in th...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.88.6.2771
更新日期:1993-12-01 00:00:00
abstract::The predictive value of the myocardial scintigraphy with 99mTc-pyrophosphate was studied in 100 patients admitted to the coronary care unit with suspected acute myocardial infarction. None of the 21 patients with normal scintigrams had acute myocardial infraction by other criteria. Fifty-five percent of patients with ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.57.2.320
更新日期:1978-02-01 00:00:00
abstract:BACKGROUND:Television viewing time, the predominant leisure-time sedentary behavior, is associated with biomarkers of cardiometabolic risk, but its relationship with mortality has not been studied. We examined the associations of prolonged television viewing time with all-cause, cardiovascular disease (CVD), cancer, an...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.109.894824
更新日期:2010-01-26 00:00:00
abstract::It has been suggested that the rate of left ventricular (LV) relaxation is related to the inotropic state, end-systolic fiber length and peak LV pressure, but little information is available regarding the rate of LV relaxation in patients with coronary artery disease (CAD) and LV dysfunction. To assess the rate of LV ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.59.5.984
更新日期:1979-05-01 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:BACKGROUND:Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality; however, no treatment is approved for this indication. We hypothesized that riociguat, a novel soluble guanylate cyclase stimulator, would have beneficial hemodynamic effects in pati...
journal_title:Circulation
pub_type: 杂志文章,随机对照试验
doi:10.1161/CIRCULATIONAHA.113.001458
更新日期:2013-07-30 00:00:00
abstract::The time of acute myocardial infarction was determined in all 1,741 patients of the ISAM (Intravenous Streptokinase in Acute Myocardial Infarction) Study, based on onset of clinical symptoms and evaluation of plasma CK-MB enzyme time-activity curves. The incidence of myocardial infarction was markedly increased betwee...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.80.4.853
更新日期:1989-10-01 00:00:00
abstract:BACKGROUND:BET (bromodomain and extraterminal) epigenetic reader proteins, in particular BRD4 (bromodomain-containing protein 4), have emerged as potential therapeutic targets in a number of pathological conditions, including cancer and cardiovascular disease. Small-molecule BET protein inhibitors such as JQ1 have demo...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.120.047239
更新日期:2020-12-15 00:00:00