Abstract:
INTRODUCTION:During and following cardiac ischemia the levels of circulating fatty acids are elevated, resulting in fatty acid oxidation dominating as a source of oxidative metabolism at the expense of pyruvate oxidation. A decrease in the levels of myocardial malonyl-CoA (an endogenous inhibitor of mitochondrial fatty acid uptake) contributes to these high fatty acid oxidation rates. Low pyruvate oxidation rates during and following ischemia results in the accumulation of metabolic byproducts (lactate and protons) that leads to impaired cardiac function, decreased cardiac efficiency, and increased myocardial tissue injury. METHODOLOGY:One approach to increasing pyruvate oxidation during and following ischemia is to inhibit fatty acid oxidation, which results in an improvement of both cardiac function and cardiac efficiency. A novel approach to decreasing fatty acid oxidation and increasing pyruvate oxidation is to increase myocardial levels of malonyl-CoA. This can be achieved by pharmacologically inhibiting malonyl-CoA decarboxylase (MCD), the principal enzyme involved in the degradation of cardiac malonyl-CoA. RESULTS:Studies with either genetic deletion of MCD in the mouse or with novel MCD inhibitors show that decreased MCD activity increases cardiac malonyl-CoA, resulting in an inhibition of fatty acid oxidation and a stimulation of pyruvate oxidation. CONCLUSION:The beneficial effects of MCD inhibition on cardiac function and cardiac efficiency suggest that this approach could be an effective means to treat ischemic heart disease.
journal_name
Cardiovasc Drugs Therjournal_title
Cardiovascular drugs and therapyauthors
Lopaschuk GD,Stanley WCdoi
10.1007/s10557-006-0634-0subject
Has Abstractpub_date
2006-12-01 00:00:00pages
433-9issue
6eissn
0920-3206issn
1573-7241journal_volume
20pub_type
杂志文章,评审abstract::Diabetic cardiomyopathy as a distinct entity was first recognized by Rubler et al. in diabetics with congestive heart failure (CHF), who had no evidence of coronary atherosclerosis. The Framingham study showed a 2.4-fold increased incidence of CHF in diabetic men and a 5.1-fold increase in diabetic women over 18 years...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877091
更新日期:1994-02-01 00:00:00
abstract::To characterize the effects of OPC-8212, a quinolone inotropic agent, in patients with heart failure, we utilized invasive hemodynamics, exercise testing, 24-hour ambulatory electrocardiograms, and two patient self-assessment questionnaires, before and after 1 month of treatment with OPC-8212, in 17 patients with mode...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00054205
更新日期:1988-12-01 00:00:00
abstract::Angiotensin-converting enzyme (ACE) inhibitor therapy has been associated with a substantial (> or = 20%) reduction in the risk of major ischemic events in two recent clinical trials with long-term follow-up: Studies of Left Ventricular Dysfunction (SOLVD) and the Survival and Ventricular Enlargement (SAVE) study. Par...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877749
更新日期:1995-02-01 00:00:00
abstract::In patients with hypertension persisting on combined diuretic and beta-blocker therapy, the effects of an additional 9-week therapy with a calcium antagonist (nifedipine) versus a classical arterial vasodilator (hydralazine) were compared for changes in blood pressure (BP), plasma catecholamines (n = 15), and left ven...
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/BF01857760
更新日期:1990-04-01 00:00:00
abstract::Piperanometozine (OPC-8212) is a new, orally effective inotropic agent. To evaluate the efficacy of this agent on systemic hemodynamics and clinical symptoms in patients with congestive heart failure, a multicenter study was performed. Thirty four patients with New York Heart Association (NYHA) functional classes II t...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/BF02125470
更新日期:1987-08-01 00:00:00
abstract::Early reperfusion after an organ ischemia is essential to salvage tissue from eventual death. However, abundant evidence suggests that reperfusion also elicits pathophysiological changes responsible for additional tissue injury after restoration of blood flow. Postconditioning (Postcon) defined as rapid sequential int...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-010-6240-1
更新日期:2010-06-01 00:00:00
abstract::Reducing elevated levels of low-density-lipoprotein cholesterol (LDL-C) significantly reduces the incidence of coronary heart disease (CHD) events and mortality in hypercholesterolemic patients. CHD risk reduction is proportional to LDL-C reduction. Despite this knowledge, many physicians are not applying existing tre...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1023/a:1013341606476
更新日期:2001-09-01 00:00:00
abstract::To evaluate cordiodepressive risks of antiarrhythmic treatment with diprafenone, we monitored, in addition to conventional hemodynamic parameters, end-systolic pressure-volume relations to assess potential negative inotropic effects. Thirteen patients underwent hemodynamic analysis with and without the influence of di...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF01883858
更新日期:1989-04-01 00:00:00
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
更新日期:2014-06-01 00:00:00
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
更新日期:1989-12-01 00:00:00
abstract::Quality of life in heart failure patients is receiving increased attention as a reflection of a treatment's potential secondary benefit of general well-being and daily functioning. The Metoprolol in Dilated Cardiomyopathy (MDC) trial was conducted as a large, multicenter trial to establish the effects of metoprolol on...
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/BF02627961
更新日期:1996-07-01 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::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: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::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
更新日期:1994-06-01 00:00:00
abstract::Unselective and beta 1-selective beta-blockers may induce vasoconstriction of normal and stenotic epicardial coronary arteries. To analyze the influence of the "vasodilatory" beta-blocker celiprolol on coronary vasomotility, 0.4 mg celiprolol/kg were intravenously infused over 4 minutes in 13 patients with coronary ar...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章
doi:10.1023/a:1007780713915
更新日期:1997-04-01 00:00:00
abstract::The purpose of the study was to determine whether a new KATP channel opener, Y 26763 (Y), can influence the electrophysiological properties in the ischemic myocardium as well as to determine whether the blunting effect of the alpha 1-adrenoceptor antagonist bunazosin (BN) on an ischemia-induced shortening of repolariz...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1007830607733
更新日期:2000-06-01 00:00:00
abstract::Heart rate variability is a noninvasive indicator of autonomic nervous system activity. The role of the autonomic nervous system in the genesis of atrial or ventricular arrhythmias is now well established. Little is known about the effects of flecainide on heart rate variability in patients with normal heart structure...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1007710301259
更新日期:1998-10-01 00:00:00
abstract:PURPOSE:The glucose-lowering drug metformin has recently been shown to reduce myocardial oxygen consumption and increase myocardial efficiency in chronic heart failure (HF) patients without diabetes. However, it remains to be established whether these beneficial myocardial effects are associated with metformin-induced ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-07050-5
更新日期:2020-08-08 00:00:00
abstract:PURPOSE:Rivaroxaban, an oral anticoagulant, undergoes the metabolism mediated by human cytochrome P450 (CYP). The present study is to quantitatively analyze and compare the contributions of multiple CYPs in the metabolism of rivaroxaban to provide new information for medication safety. METHODS:The metabolic stability ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-07129-z
更新日期:2021-01-07 00:00:00
abstract::Early reperfusion represents the key strategy in ST elevation myocardial infarction. However, reperfusion may induce myocardial damage due to the reperfusion myocardial injury, compromising the full potential of reperfusion therapy and accounting for unfavourable results in high risk patients. Adenosine seems to atten...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-015-6606-5
更新日期:2015-01-01 00:00:00
abstract:AIM:To study the relationship between Daxx expression and the antiapoptotic effects of probucol in THP-1 macrophage. MATERIALS AND METHODS:Apoptosis of THP-1 derived macrophages was induced by exposure to oxidized low density lipoprotein (oxLDL). The development of apoptosis was determined by flow cytometry analysis a...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-007-6002-x
更新日期:2007-02-01 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 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::We studied the acute and chronic effects of propionyl-L-carnitine (PLC) on mechanical function of isolated rabbit heart. Propionyl-L-carnitine was either directly delivered in the perfusate (10(-9) to 10(-3) M) or intraperitoneally injected (250 mg/kg) for 10 days to the animals. When added acutely, propionyl-L-carnit...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF00128239
更新日期:1991-02-01 00:00:00
abstract::A survey of the pharmacokinetic properties of the three prototypical calcium antagonist agents shows that they have in common a very high rate of hepatic first-pass metabolism with, in the case of verapamil and diltiazem, the formation of an active metabolite that affects the dose during chronic therapy. Therefore, th...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF01865507
更新日期:1989-08-01 00:00:00
abstract:BACKGROUND:Although Takotsubo syndrome (TS) was once considered to be rare and largely benign, it is now recognized to represent a major cause of cardiac morbidity and mortality, especially in ageing women. The biochemical precipitant of attacks of TS is an increase in catecholamine concentrations within the myocardium...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-019-06918-5
更新日期:2020-02-01 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::Recent surveys in the U.S. have reported, for the first time, that a significant number of patients with hypertension are finding that the cost of medication and treatment in general is an obstacle to treatment. The cost of management of hypertension can be contained if: a) the diagnostic workup is kept simple (this d...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF01857624
更新日期:1989-10-01 00:00:00
abstract:PURPOSE:Although the role of angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension has been well established, no data has been generated regarding the influence of ACE inhibitors for health-related quality-of-life (QOL) dimensions for Chinese patients. MATERIALS:A double-blind, active-contro...
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:1020648405680
更新日期:2002-05-01 00:00:00