Aleglitazar, a Balanced Dual PPARα and -γ Agonist, Protects the Heart Against Ischemia-Reperfusion Injury.

Abstract:

PURPOSE:To evaluate whether aleglitazar (Ale), a dual PPARα/γ agonist, has additive effects on myocardial protection against ischemia-reperfusion injury. METHODS:Human cardiomyocytes (HCMs), cardiomyocytes from cardiac-specific PPARγ knockout (MCM-PPARγ (CKO) ) or wild type (MCM-WT) mice were incubated with different concentrations of Ale, and subjected to simulated ischemia-reperfusion (SIR) or normoxic conditions (NSIR). Cell viability, apoptosis and caspase-3 activity were determined. HCMs were transfected with siRNA against PPARα (siPPARα) or PPARγ (siPPARγ) followed by incubation with Ale. PPARα/γ DNA binding capacity was measured. Cell viability, apoptosis and levels of P-AKT and P-eNOS were assessed. Infarct size following 30 min coronary artery occlusion and 24 h reperfusion were assessed in WT and db/db diabetic mice following 3-day pretreatment with vehicle, Ale or glimeperide. RESULTS:Ale (at concentrations of 150-600 nM) increased cell viability and reduced apoptosis in HCMs, MCM-WT and MCM-PPAR (CKO) exposed to SIR. In HCM, the protective effect was partially blocked by siPPARα alone or siPPARγ alone, and completely blocked by siPPARα+siPPARγ. Ale increased P-Akt/P-eNOS in HCMs. P-Akt or P-eNOS levels were decreased when PPARα alone, PPARγ alone and especially when both were knocked down. Peritoneal GTTs revealed that db/db mice had developed impaired glucose tolerance and insulin sensitivity, which were normalized by Ale or glimepiride treatment. Ale, but not glimepiride, limited infarct size in both WT and diabetic mice after ischemia-reperfusion. CONCLUSIONS:Ale protects against myocardial apoptosis caused by hypoxia-reoxygenation in vitro and reduces infarct size in vivo.

journal_name

Cardiovasc Drugs Ther

authors

Qian J,Chen H,Birnbaum Y,Nanhwan MK,Bajaj M,Ye Y

doi

10.1007/s10557-016-6650-9

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

129-41

issue

2

eissn

0920-3206

issn

1573-7241

pii

10.1007/s10557-016-6650-9

journal_volume

30

pub_type

杂志文章
  • The applied pharmacology of beta-adrenoceptor antagonists (beta blockers) in relation to clinical outcomes.

    abstract::Despite the fact that beta blockers were introduced into clinical practice 25 years ago, new beta blockers with differing kinetic and dynamic profiles continue to be developed and marketed. This overview assesses some of the more extensively studied agents from the point of view of proof of utility and the validity of...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,评审

    doi:10.1007/BF03029726

    authors: Fitzgerald JD

    更新日期:1991-06-01 00:00:00

  • The problem of defining heart failure.

    abstract::A succession of theories arising from last century has attempted to explain why patients with damaged hearts develop peripheral edema. Opposed to the original simple concepts of backward failure, a number of theories of forward failure have been proposed, the cardiac output being considered inadequate for capillary pe...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,评审

    doi:10.1007/BF00877921

    authors: Harris P

    更新日期:1994-06-01 00:00:00

  • Recovery of left ventricular function following early reperfusion in acute myocardial infarction: a potential role for the calcium antagonist nisoldipine.

    abstract::The purpose of the present study was to test whether the administration of a vascular-selective organic calcium antagonist (nisoldipine) at the onset of early mechanical reperfusion (by coronary angioplasty) in acute myocardial infarction could prevent or attenuate postischemic stunning and enhance the recovery of lef...

    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:1007713118941

    authors: Sheiban I,Tonni S,Chizzoni A,Marini A,Trevi G

    更新日期:1997-03-01 00:00:00

  • Intracoronary administration of adenosine triphosphate increases coronary blood flow and attenuates the severity of myocardial ischemic injury in dogs.

    abstract::ATP generates nitric oxide (NO) via activation of P2y receptors, and is degraded to adenosine. This study was undertaken to examine whether ATP causes coronary hyperemic flow via purinoceptors-, NO- and adenosine-dependent mechanisms, and attenuates the severity of contractile and metabolic dysfunction in the ischemic...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章

    doi:10.1023/a:1007899822136

    authors: Kitakaze M,Node K,Komamura K,Minamino T,Kosaka H,Kuzuya T,Hori M

    更新日期:1999-09-01 00:00:00

  • Effect of an educational program (PEGASE) on cardiovascular risk in hypercholesterolaemic patients.

    abstract:BACKGROUND:Many studies have demonstrated a gap between guidelines for the prevention of cardiovascular disease (CVD) and their implementation in clinical practice. AIM:The PEGASE education program has been devised with an aim to improve the management of patients at high risk of CVD. METHODS:In a multicentre study c...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1007/s10557-008-6137-4

    authors: Bruckert E,Giral P,Paillard F,Ferrières J,Schlienger JL,Renucci JF,Abdennbi K,Durack I,Chadarevian R,PEGASE group.

    更新日期:2008-12-01 00:00:00

  • When is discontinuation of antihypertensive therapy indicated?

    abstract::Major advances have been established in the handling of hypertensive vascular disease in recent years. However, drug compliance, drug costs, and the side effects of antihypertensive agents have prompted the question of whether intermittent therapy or even possible removal of medication represents an alternative to lif...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,评审

    doi:10.1007/BF02026496

    authors: Schmieder RE,Rockstroh JK

    更新日期:1990-12-01 00:00:00

  • Effect of the cardioselective, sarcolemmal K(ATP) channel blocker HMR 1098 on atrial electrical remodeling during pacing-induced atrial fibrillation in dogs.

    abstract:PURPOSE:The progressive shortening of the atrial effective refractory period (ERP) during atrial fibrillation (AF) might be due to the activation of the KATP channels by rapid atrial rates. We tested the hypothesis that the cardioselective, sarcolemmal KATP channel blocker HMR 1098 would prevent atrial ERP shortening d...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章

    doi:10.1023/B:CARD.0000025752.63337.b2

    authors: Vereckei A,Gögelein H,Wirth KJ,Zipes DP

    更新日期:2004-01-01 00:00:00

  • Enoximone: true inotropic effects? Do they cause ischemia? Analysis of end-systolic pressure-volume relations using the conductance (volume) catheter technique.

    abstract::True positive inotropy of enoximone is hard to prove clinically. It could increase the risk of myocardial ischemia when used in coronary artery disease (CAD). The analysis of the end-systolic pressure-volume relationship (ESPVR) as a load-independent parameter of the contractile left ventricular function (LVF) allows ...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章

    doi:10.1007/BF02018269

    authors: Thormann J,Hueting J,Kremer P,Wissemann J,Mitrovic V,Dieterich HA,Schlepper M

    更新日期:1990-10-01 00:00:00

  • Antiischemic effects of nicorandil during coronary angioplasty in humans.

    abstract::The present study was undertaken on 10 patients with angina undergoing percutaneous transluminal coronary angioplasty. The angioplasty procedure consisted of two successive 30-second balloon inflations at 5 minute intervals. After the first inflation, nicorandil (0.1 mg/kg) was given intravenously over a 2-minute peri...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00878473

    authors: Saito S,Mizumura T,Takayama T,Honye J,Fukui T,Kamata T,Moriuchi M,Hibiya K,Tamura Y,Ozawa Y

    更新日期:1995-03-01 00:00:00

  • Effects of trimetazidine on in vivo coronary arterial platelet thrombosis.

    abstract::We used Folts' model of critical coronary artery stenosis with endothelial damage, which measures platelet-rich thrombus accumulation from cyclic flow reductions (CFRs). This paper reports results applied to trimetazidine, a member of the piperazine group. Trimetazidine at a dose of 1 mg/kg completely abolished CFRs c...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章

    doi:10.1007/BF00878324

    authors: Belcher PR,Drake-Holland AJ,Hynd JW,Noble MI

    更新日期:1993-02-01 00:00:00

  • Cardiovascular and renal surrogate markers in the clinical management of hypertension.

    abstract:INTRODUCTION:Surrogate markers represent a significant contribution to early diagnosis, longitudinal prognoses, and outcome prediction in cases of hypertension. They often enable detection of disease and disease potential when the disease is still subclinical and are useful noninvasive tools for designing and evaluatin...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,评审

    doi:10.1007/s10557-009-6177-4

    authors: Maisel AS

    更新日期:2009-08-01 00:00:00

  • Correction to: Do Limitations in the Design of PARADIGM-HF Justify the Slow Real World Uptake of Sacubitril/Valsartan (Entresto)?

    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

    authors: Ahn R,Prasad V

    更新日期:2018-12-01 00:00:00

  • Alterations in the prognosis of chronic heart failure: an overview of the major mortality trials.

    abstract::Treatment of chronic heart failure (CHF) remains a major medical problem. Although in the last decades the benefits of several therapies in different patient populations with left ventricular dysfunction have been established, morbidity and mortality of CHF patients are high. Consequently, in the last decade improveme...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,meta分析

    doi:10.1023/a:1007786019054

    authors: Szabó BM,van Veldhuisen DJ,de Graeff PA,Lie KI

    更新日期:1997-07-01 00:00:00

  • Effect of colesevelam HCl monotherapy on lipid particles in type 2 diabetes mellitus.

    abstract:PURPOSE:In addition to lowering hemoglobin A1C, colesevelam has been shown to improve the atherogenic lipoprotein profile of subjects with type 2 diabetes mellitus (T2DM) when used in combination with metformin and/or sulfonylureas. A recent study evaluated the effects of colesevelam as antidiabetes monotherapy in adul...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1007/s10557-014-6516-y

    authors: Rosenson RS,Rigby SP,Jones MR,Chou HS

    更新日期:2014-06-01 00:00:00

  • Ibopamine versus hydrochlorothiazide/amiloride in patients with mild congestive heart failure. SK & F Ibopamine Working Group.

    abstract::The clinical efficacy and safety of ibopamine and diuretic therapy were compared in a multicenter, multinational, parallel, positive-controlled, randomized, double-blind, 12-week study, involving 103 patients with mild CHF (NYHA Class II). Body weight, NYHA functional class, symptom assessment scores, laboratory blood...

    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/BF01869579

    authors:

    更新日期:1989-12-01 00:00:00

  • Roles of hepatocyte growth factor and mast cells in thrombosis and angiogenesis.

    abstract::Concentrations of the circulating hepatocyte growth factor (HGF) increase in the very early phase of acute myocardial infarction, and are a marker of arterial thrombosis. A recently developed, highly sensitive HGF assay can detect the early stages of arterial thrombosis in patients with unstable angina pectoris, acute...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,评审

    doi:10.1023/B:CARD.0000041252.33870.74

    authors: Matsumori A

    更新日期:2004-07-01 00:00:00

  • Evaluation of the functional status questionnaire in heart failure: a sub-study of the second cardiac insufficiency bisoprolol survival study (CIBIS-II).

    abstract:AIMS:We evaluated a generic quality of life (QoL) Functional Status Questionnaire (FSQ), in patients with chronic heart failure (CHF). The FSQ assesses the 3 main dimensions of QoL: physical functioning, mental health and social role. It also includes 6 single item questions about: work status, frequency of social inte...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s10557-011-6284-x

    authors: Gallanagh S,Castagno D,Wilson B,Erdmann E,Zannad F,Remme WJ,Lopez-Sendon JL,Lechat P,Follath F,Höglund C,Mareev V,Sadowski Z,Seabra-Gomes RJ,Dargie HJ,McMurray JJ

    更新日期:2011-02-01 00:00:00

  • Carbachol prolongs ventricular repolarisation through nitric oxide release in an intact heart.

    abstract:AIMS:The primary ain of this study was to investigate the effect of carbachol on ventricular repolarisation in an intact animal heart. METHODS:In five sheep, carbachol was administered to the left circumflex coronary artery (LCX) at 1.0 and 2.5 micromol/ml/min respectively for 3 min. Multiple unipolar ECGs were acquir...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章

    doi:10.1023/a:1027324412869

    authors: Wang L

    更新日期:2003-07-01 00:00:00

  • Racial differences in antihypertensive therapy: evidence and implications.

    abstract::Blood pressure is controlled by many factors, and thus hypertension is a multifactorial disorder. This etiologic diversity is also reflected in the broad spectrum of different pharmacologic agents known to lower blood pressure. Most carefully controlled studies employing a single antihypertensive drug in unselected, u...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,评审

    doi:10.1007/BF02603180

    authors: Weinberger MH

    更新日期:1990-03-01 00:00:00

  • The economic efficiency of amlodipine in the treatment of coronary atherosclerosis--an analysis based on the PREVENT study.

    abstract:BACKGROUND:High health service expenditure on the one hand, and the politically declared objective of stability of statutory contributions and restriction of public funds on the other hand, have been central points of the political and social discussion for several years. The over-proportional increase in health servic...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章

    doi:10.1023/a:1015323700206

    authors: Cathomas G,Erne P,Schwenkglenks M,Szucs TD

    更新日期:2002-01-01 00:00:00

  • LOX-1 and obesity.

    abstract::Obesity is one of the most common lifestyle-related diseases. Being closely associated with insulin resistance, hypertension and dyslipidemia, it is also a component of metabolic syndrome and is involved in the development of atherosclerosis and cardiovascular and renal ailments. Obesity is also accompanied with a sta...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,评审

    doi:10.1007/s10557-011-6335-3

    authors: Yan M,Mehta JL,Hu C

    更新日期:2011-10-01 00:00:00

  • Comparison of the efficacy of atenolol and its combination with slow-release nifedipine in chronic stable angina.

    abstract::There is still uncertainty of whether combined therapy with a beta-blocker and calcium-channel antagonist provides additive or synergistic clinical benefits in most patients with stable angina pectoris. The comparative antianginal effect of atenolol 50 mg and atenolol 50 mg and slow release nifedipine (20 mg) twice a ...

    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/BF00877726

    authors: Meyer TE,Adnams C,Commerford P

    更新日期:1993-12-01 00:00:00

  • Levosimendan in Acute and Advanced Heart Failure: an Expert Perspective on Posology and Therapeutic Application.

    abstract::Levosimendan, a calcium sensitizer and potassium channel-opener, is widely appreciated by many specialist heart failure practitioners for its effects on systemic and pulmonary hemodynamics and for the relief of symptoms of acute heart failure. The drug's impact on mortality in large randomized controlled trials has be...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,评审

    doi:10.1007/s10557-018-6838-2

    authors: Bouchez S,Fedele F,Giannakoulas G,Gustafsson F,Harjola VP,Karason K,Kivikko M,von Lewinski D,Oliva F,Papp Z,Parissis J,Pollesello P,Pölzl G,Tschöpe C

    更新日期:2018-12-01 00:00:00

  • Heart rate and heart rate variability, a pharmacological target.

    abstract::Heart rate varies with respiration, blood pressure, emotion, etc., and heart rate variability (HRV) is presently one of the best indices to predict fatal issues in cardiac failure and after myocardial infarction. HRV depends on various reflexes. In addition, parallel studies of HRV and the myocardial adrenergic and mu...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,评审

    doi:10.1007/BF00053024

    authors: Swynghedauw B,Jasson S,Chevalier B,Clairambault J,Hardouin S,Heymes C,Mangin L,Mansier P,Médigue C,Moalic JM,Thibault N,Carré F

    更新日期:1997-01-01 00:00:00

  • Modulatory effect of fenofibrate on endothelial production of neutrophil chemokines IL-8 and ENA-78.

    abstract:PURPOSE:The PPAR-alpha agonists (fibrates) are commonly used in the treatment of dyslipidemia. It has been hypothesized that the cardio-protective effects of fibrates are partially due to immunomodulatory effects. However, there is a paucity of data regarding the effect of fibrates on neutrophilic chemokines such as ep...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章

    doi:10.1007/s10557-011-6368-7

    authors: Price ET,Welder GJ,Zineh I

    更新日期:2012-04-01 00:00:00

  • Key factors in the treatment of the elderly hypertensive.

    abstract::Cardiovascular diseases are of fundamental importance in the cause of death and morbidity in the elderly as a group. If the successful management of blood pressure can effect a reduction in morbid events as well as death, as has been indicated by recent trials, the elderly have more to gain than any other group within...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章,评审

    doi:10.1007/BF00114231

    authors: Dall JL

    更新日期:1991-01-01 00:00:00

  • A systemic combination therapy with granulocyte-colony stimulating factor plus erythropoietin aggravates the healing process of balloon-injured rat carotid arteries.

    abstract:OBJECTIVE:Percutaneous vascular interventions lead inevitably to a destruction of the endothelial lining at the site of injury. There are conflicting data on the therapeutic benefit of hematopoietic growth factors aiming at mobilisation of circulating endothelial cells to accelerate the reendothelialisation process. Ai...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章

    doi:10.1007/s10557-008-6117-8

    authors: Hack M,Mascha FG,Jobst BJ,Riegger GA,Griese DP

    更新日期:2008-10-01 00:00:00

  • Anti-arrhythmic effects of I (Na), I (Kr), and combined I (Kr)-I (CaL) blockade in an experimental model of acute stretch-related atrial fibrillation.

    abstract:INTRODUCTION:Atrial dilatation is commonly associated with atrial fibrillation (AF), but the electrophysiological mechanisms and the implications for anti-arrhythmic therapy are poorly understood. In a model of acute stretch-related AF in isolated rabbit hearts, we evaluated the electrophysiological effects of three di...

    journal_title:Cardiovascular drugs and therapy

    pub_type: 杂志文章

    doi:10.1007/s10557-007-6001-y

    authors: Kalifa J,Bernard M,Gout B,Bril A,Cozma D,Laurent P,Chalvidan T,Deharo JC,Djiane P,Cozzone P,Maixent JM

    更新日期:2007-02-01 00:00:00

  • Glucose-insulin-potassium (GIK) for acute myocardial infarction: a negative study with a positive value.

    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

    authors: Apstein CS,Opie LH

    更新日期:1999-05-01 00:00:00

  • Lisinopril in the treatment of congestive heart failure in elderly patients: comparison versus captopril.

    abstract::The present study was performed in order to compare the efficacy, safety, and tolerability of lisinopril, a long-acting angiotensin-converting enzyme (ACE) inhibitor, with captopril, the shorter acting ACE inhibitor available, in the treatment of elderly patients (mean age 70 +/- 0.5 years) with congestive heart failu...

    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:1007704024393

    authors: Morisco C,Condorelli M,Crepaldi G,Rizzon P,Zardini P,Villa G,Argenziano L,Trimarco B

    更新日期:1997-03-01 00:00:00