Abstract:
PURPOSE:Homocysteine (Hcy) is an independent risk factor for cardiovascular diseases that impairs endothelial function. We investigated whether the impaired endothelial function can be restored by the eNOS transcription enhancer AVE3085 in porcine coronary arteries. The effects of AVE3085 against Hcy on eNOS-NO function were studied and further investigations were conducted to reveal the role of arginase and the signaling pathway of eNOS activation in the effect of AVE3085 on endothelial dysfunction caused by Hcy. METHODS:Myograph study of vasorelaxation, electrochemical measurement of NO, RT-PCR and Western blot analysis of eNOS, iNOS expression, and eNOS phosphorylation were performed. Arginase activity was determined by urea production and O2 (.-) generation by lucigenin-enhanced chemiluminenscence. RESULTS:Exposure to Hcy for 24 h attenuated bradykinin-induced relaxation and NO release, downregulated eNOS mRNA expression and protein expressions of eNOS and p-eNOS(Ser1177) whereas it upregulated iNOS expression. AVE3085 restored NO release and relaxation, enhanced eNOS but decreased iNOS expression. Inhibition of protein kinase Akt or PI3 kinase attenuated the effect of AVE3085 on relaxation and eNOS phosphorylation. Arginase activity and O2 (.-) production were inhibited by AVE3085 in Hcy-exposed vessels. CONCLUSIONS:AVE3085 prevents Hcy-induced endothelial dysfunction in coronary arteries by preservation of NO production and suppression of O2 (.-) generation. Preservation of NO is attributed to upregulation of eNOS expression, activation of eNOS via phosphorylation of Ser1177 through a PI3 kinase/Akt-dependent pathway, and inhibition of arginase. Reduction of O2 (.-) generation results from reversal of eNOS uncoupling and inhibition of arginase and iNOS.
journal_name
Cardiovasc Drugs Therjournal_title
Cardiovascular drugs and therapyauthors
Yang Q,Xue HM,Underwood MJ,Yu CMdoi
10.1007/s10557-013-6478-5subject
Has Abstractpub_date
2013-12-01 00:00:00pages
511-20issue
6eissn
0920-3206issn
1573-7241journal_volume
27pub_type
杂志文章abstract:PURPOSE:Treatment of pulmonary arterial hypertension (PAH) by vasodilator drug monotherapy is often limited in its effectiveness. Combination therapy may help to improve treatment and to reduce drug toxicity. This study assessed the combination of the endothelin receptor antagonist macitentan and the phosphodiesterase-...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-019-06868-y
更新日期:2019-06-01 00:00:00
abstract::Resistance arteries depolarize and constrict to elevations in intravascular pressure. However, many of the molecular aspects of this phenomenon are not known. We present evidence that large conductance calcium-dependent potassium (KCa) channels, which are activated by intracellular calcium and membrane depolarization,...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877627
更新日期:1993-08-01 00:00:00
abstract::Beneficial effects of monotherapy with ACE inhibitors or beta-blockers on hemodynamic function after myocardial infarction are well known. Until now, the effects of combined treatment on cardiac function and energy metabolism have been poorly described. This study examines the effects of combined ramipril and metoprol...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1007846311040
更新日期:2000-12-01 00:00:00
abstract:PURPOSE:We tested if inhibition of phosphodiesterases (PDEs) with IBMX (1-methyl-3-isobutylxanthine) can modulate the mitochondrial permeability transition pore (mPTP) opening by inactivating glycogen synthase kinase 3β (GSK-3β). METHODS:H9c2 cells were exposed to 600 μM H(2)O(2) for 20 min to cause the mPTP opening. ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-011-6310-z
更新日期:2011-08-01 00:00:00
abstract::The hypothesis tested was that enhanced entry of calcium into cardiac cells would increase the susceptibility to ventricular fibrillation as measured by the ventricular fibrillation threshold (VFT) of the isolated perfused rat heart. Bay-K-8644 was used as a calcium-channel agonist. There was a biphasic effect with a ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00052561
更新日期:1992-12-01 00:00:00
abstract::The novel insights provided by the molecular genetic applied to the study of cardiac arrhythmias have just started to scratch the surface of the complex relationships between the genetic abnormalities of ion channel structure and the susceptibility to life threatening ventricular arrhythmias. These crucial pieces of i...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1023/a:1015793113771
更新日期:2002-03-01 00:00:00
abstract::The purpose of this study was to evaluate the effect of trimetazidine on late potentials in patients with acute myocardial infarction. A total of 60 patients (52 males, mean age 55 +/- 2 years, and 8 females, mean age 54 +/- 1.8 years) with the diagnosis of acute myocardial infarction were included in this study. The ...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1007740311072
更新日期:1999-04-01 00:00:00
abstract::With the increased use of long-acting nitroglycerin preparations, there has been greater recognition of the problem of nitrate tolerance. In recent years extensive research has broadened our understanding of the mechanisms of nitroglycerin action and the mechanisms of drug attenuation. This paper reviews the current s...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF01857640
更新日期:1990-02-01 00:00:00
abstract::Ranolazine, an inhibitor of the late current of the cardiac action potential (late I(Na)), is a well established clinical treatment for chronic angina. The late INa in cardiac myocytes also plays an important role in the pathophysiology of acute myocardial ischemia and reperfusion, and thus is a potential therapeutic ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-014-6548-3
更新日期:2014-10-01 00:00:00
abstract:PURPOSE:For patients with heart failure with reduced ejection fraction (HFrEF), guidelines recommend use of beta-blockers with gradual up-titration. However, many patients with HFrEF do not use beta-blockers and up-titration is rare. Our purpose was to identify and rank barriers to beta-blocker use and up-titration fro...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-017-6764-8
更新日期:2017-12-01 00:00:00
abstract:PURPOSE:The melatonin receptor (MT) agonist ramelteon has a higher affinity to MT1 than for MT2 receptors and induces cardioprotection by involvement of mitochondrial potassium channels. Activation of mitochondrial potassium channels leads to release of free radicals. We investigated whether (1) ramelteon-induced cardi...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-06972-4
更新日期:2020-06-01 00:00:00
abstract::The antihypertensive effects of once-daily administration of celiprolol 400 mg were compared with those of once-daily enalapril 20 mg in 20 mild to moderate essential hypertensives in a single-blind study in which the subjects were randomized to 2 weeks' treatment with either drug, preceded by 2 weeks of placebo admin...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00051236
更新日期:1988-07-01 00:00:00
abstract::When severely ischemic myocardium is reperfused, prolonged myocardial dysfunction--a phenomenon named myocardial stunning--frequently occurs. Stunning also occurs in a variety of other situations. These include myocardium located adjacent to infarcted tissue, transient increase in myocardial O2 demands in the presence...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00053546
更新日期:1991-10-01 00:00:00
abstract::The effects of equipotent concentrations of diltiazem, verapamil, and nifedipine upon the accumulation of extracellular potassium [K+]out and the left ventricular pressure (LVP) were studied during global ischemia in isolated perfused rat hearts. Measurement of [K+]out and LVP were performed in two series of experimen...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00143532
更新日期:1991-12-01 00:00:00
abstract::Despite continuous advances in myocardial revascularization procedures and intracoronary devices, patients with ischemic heart disease (IHD) still experience worse prognosis and poor quality of life (QoL). Indeed, chronic stable angina (CSA) is a common disease with a large burden on healthcare costs. Traditionally, C...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-016-6677-y
更新日期:2016-08-01 00:00:00
abstract::The original version of this article unfortunately contained a mistake. There was a typo in the second sentence of the paragraph under the section Was the Dose of Drugs Fair?; "320 mg twice a day" should read "160mg twice a day". The corrected paragraph is shown below. ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,已发布勘误
doi:10.1007/s10557-018-6834-6
更新日期:2018-12-01 00:00:00
abstract::We compared the time-course of the hemodynamic effect of isosorbide dinitrate (ISDN), 5 mg, in the form of sublingual tablet and oral spray, in 15 patients with isolated chronic pulmonary congestion (pulmonary arterial end-diastolic pressure of 15 mmHg or more in the presence of normal or only slightly reduced cardiac...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00051192
更新日期:1988-11-01 00:00:00
abstract::Cardiovascular disease is the leading cause of death in men and women in the USA. Once a patient experiences an acute coronary syndrome (ACS), they are at increased risk for hospital readmission within 30 days and 6 months after discharge and more importantly, they have worse survival. Hospital readmissions lead to po...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-018-6798-6
更新日期:2018-12-01 00:00:00
abstract::Excess activity of the sympathetic nervous system (SNS) is linked to human obese hypertension and to salt-sensitive hypertension. Paradoxically, reduced SNS activity has been implicated as a contributor to obesity, particularly in animal models, and salt loading usually inhibits SNS activity. We have investigated the ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00120497
更新日期:1996-06-01 00:00:00
abstract:PURPOSE:The ischemic/bleeding trade-off of continuing dual antiplatelet therapy (DAPT) beyond 1 year after PCI for patients with high thrombotic risk (HTR) as endorsed by 2018 ESC/EACTS myocardial revascularization guidelines remain unknown. METHODS:Patients undergoing coronary stenting between January 2013 and Decemb...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-07030-9
更新日期:2020-10-01 00:00:00
abstract::Preconditioning and stunning are the chief adaptive changes induced in myocardium by a brief episode of reversible ischemia followed by arterial reperfusion. In the dog heart, both coexist for a period of at least 20 minutes of reperfusion, but after 120 minutes of reflow, preconditioning is much diminished, while stu...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00053555
更新日期:1991-10-01 00:00:00
abstract:PURPOSE:Hypothyroidism (HT) is associated with accelerated atherosclerosis (AS). The efficacy of traditional strategies of hypothyroid AS remains controversial. Here, we aimed to deepen the understanding of the HT-induced acceleration of AS, to decrease the residual risk of coronary artery disease (CAD) and to find a n...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-06996-w
更新日期:2020-06-03 00:00:00
abstract::This article considers the dominant role of trials involving thousands of patients--the mega-trials--in cardiovascular disease. Problems with large trials mean that alternative strategies must be developed to aid the introduction of new drugs. The limitations of meta-analysis, and of trials with combined and surrogate...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00053034
更新日期:1997-01-01 00:00:00
abstract::Beta-blocker-induced benefit in heart failure is under intense evaluation. Several large-scale mortality trials are currently being performed, with CIBIS II evaluating bisoprolol. The economic impact of beta-blocker therapy in heart failure has not been previously determined. The present study is a cost-effectiveness ...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1023/a:1007773901631
更新日期:1998-07-01 00:00:00
abstract::The efficacy of a fixed combination of 10 mg nifedipine and 100 mg acebutolol was tested in 21 patients with angiographically proven coronary artery disease (CAD). Ejection fraction (EF), emptying and filling rate (VS and VD), and end-systolic volume (ESV) were assessed by means of radionuclide ventriculography at res...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00148473
更新日期:1989-06-01 00:00:00
abstract::Glucose-insulin-therapy for acute myocardial infarction (AMI) has had a long history, going back 37 years to the pioneering concepts of Sodi-Pallares. Although a recent meta-analysis of a number of smaller trials has suggested mortality benefit, it is only the South American trial, published in Circulation in 1998, th...
journal_title:Cardiovascular drugs and therapy
pub_type: 评论,社论,评审
doi:10.1023/a:1007757407246
更新日期:1999-05-01 00:00:00
abstract::Male Japanese white rabbits were fed a restricted amount (100 g/head/day) of an atherogenic diet containing 0.2% cholesterol and 6% peanut oil during an 8-week experimental period. Atherosclerotic lesions, characterized by intimal thickening with lipid deposition, were produced by de-endothelialization of the rabbit a...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00878516
更新日期:1993-04-01 00:00:00
abstract::In vitro and in vivo studies have demonstrated many similarities between the three calcium antagonists verapamil, nifedipine, and diltiazem in relation to protection of the myocardium during hypoxia. Important clinical differences exist between the three drugs when they are used during or after an acute myocardial inf...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF03029738
更新日期:1991-08-01 00:00:00
abstract::Though the exact physiology and pathology of lipoprotein(a) [Lp(a)] remains unknown, it has been demonstrated that increased serum Lp(a) levels are correlated with an increased risk of atherosclerotic vascular disease. The effects of lipid-lowering drugs on Lp(a) levels is unclear because of inconsistencies between st...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/BF00878550
更新日期:1995-10-01 00:00:00
abstract:PURPOSE:The mitogen-activated protein kinase phosphatases (MKPs) are a family of dual-specificity phosphatases that inactivate MAPKs by dephosphorylation. Impairment of MKP-1 expression in insulin resistance has been suggested to affect the cardioprotective properties of insulin. We hypothesized that manipulation of it...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-017-6731-4
更新日期:2017-06-01 00:00:00