Abstract:
PURPOSE:The glucagon-like peptide-1 (GLP-1) has been shown to exert cardioprotective effects in animals and patients. This study tests the hypothesis that preservation of GLP-1 by the GLP-1 receptor agonist liraglutide or the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin is associated with a reduction of angiotensin (Ang) II-induced cardiac fibrosis. METHODS AND RESULTS:Sprague-Dawley rats were subjected to Ang II (500 ng/kg/min) infusion using osmotic minipumps for 4 weeks. Liraglutide (0.3 mg/kg) was subcutaneously injected twice daily or linagliptin (8 mg/kg) was administered via oral gavage daily during Ang II infusion. Relative to the control, liraglutide, but not linagliptin decreased MAP (124 ± 4 vs. 200 ± 7 mmHg in control, p < 0.003). Liraglutide and linagliptin comparatively reduced the protein level of the Ang II AT1 receptor and up-regulated the AT2 receptor as identified by a reduced AT1/AT2 ratio (0.4 ± 0.02 and 0.7 ± 0.01 vs. 1.4 ± 0.2 in control, p < 0.05), coincident with the less locally-expressed AT1 receptor and enhanced AT2 receptor in the myocardium and peri-coronary vessels. Both drugs significantly reduced the populations of macrophages (16 ± 6 and 19 ± 7 vs. 61 ± 29 number/HPF in control, p < 0.05) and α-SMA expressing myofibroblasts (17 ± 7 and 13 ± 4 vs. 66 ± 29 number/HPF in control, p < 0.05), consistent with the reduction in expression of TGFβ1 and phospho-Smad2/3, and up-regulation of Smad7. Furthermore, ACE2 activity (334 ± 43 and 417 ± 51 vs. 288 ± 19 RFU/min/μg protein in control, p < 0.05) and GLP-1 receptor expression were significantly up-regulated. Along with these modulations, the synthesis of collagen I and tissue fibrosis were inhibited as determined by the smaller collagen-rich area and more viable myocardium. CONCLUSION:These results demonstrate for the first time that preservation of GLP-1 using liraglutide or linagliptin is effective in inhibiting Ang II-induced cardiac fibrosis, suggesting that these drugs could be selected as an adjunctive therapy to improve clinical outcomes in the fibrosis-derived heart failure patients with or without diabetes.
journal_name
Cardiovasc Drugs Therjournal_title
Cardiovascular drugs and therapyauthors
Zhang LH,Pang XF,Bai F,Wang NP,Shah AI,McKallip RJ,Li XW,Wang X,Zhao ZQdoi
10.1007/s10557-015-6592-7subject
Has Abstractpub_date
2015-06-01 00:00:00pages
243-55issue
3eissn
0920-3206issn
1573-7241journal_volume
29pub_type
杂志文章abstract::Milrinone is shown in 10 patients to be a valuable pharmacological bridge to heart transplantation; it can stabilize and improve decompensated chronic heart failure (CHF) in cases where the response to beta-agonists is inadequate. One patient who had suffered an acute myocardial infarction with heart failure resistant...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877820
更新日期:1993-08-01 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:PURPOSE:A multicentre, randomized, double-blind, placebo-controlled, parallel-group study aimed to define the potential positive effect of dipeptidyl peptidase-4 inhibition on left ventricular systolic function (LVSF) beyond glycemic control in type 2 diabetes mellitus (T2DM) (DYDA 2™ trial). METHODS:Individuals with ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-019-06898-6
更新日期:2019-10-01 00:00:00
abstract::The combination of aspirin and clopidogrel is the mainstay antiplatelet therapy for acute coronary syndromes (ACS). However, the dosing of aspirin, the dosing of clopidogrel, the timing of clopidogrel initiation as well as the duration of clopidogrel therapy remain controversial matters. Clopidogrel resistance is an e...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-009-6212-5
更新日期:2010-02-01 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::Despite the impressive relation between an increased blood cholesterol and increased mortality from coronary artery disease and despite the persuasive results of cholesterol-lowering trials in secondary prevention, there are increasing reservations about the wisdom of lowering moderately raised blood cholesterol level...
journal_title:Cardiovascular drugs and therapy
pub_type: 社论
doi:10.1007/BF00878930
更新日期:1993-11-01 00:00:00
abstract::Intravenous amiodarone has been found useful in the emergent management of life-threatening arrhythmias. Experimental studies have shown that its electrophysiologic effects are proportional to its myocardial concentration. However, early after its intravenous administration, the extent of the concentration of amiodaro...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1023/a:1007756411790
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND:The use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) is currently expanding to cardiovascular risk reduction in non-diabetic subjects, but renal (side-)effects are less well studied in this setting. METHODS:Male non-diabetic Sprague Dawley rats underwent permanent coronary artery ligation to induc...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-06954-6
更新日期:2020-06-01 00:00:00
abstract:PURPOSE:Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Azelnidipine is a novel dihydropyridine calcium channel blocker. Several studies have demonstrated that some dihydropyridine calcium channel blockers have antioxidant effects. We evaluated the antioxidant effects of azelnid...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-007-6008-4
更新日期:2007-02-01 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::This study compares the electrophysiologic effects of amlodipine and diltiazem in patients with coronary artery disease concomitantly treated with background beta-blocking therapy. Thirty patients were included in an open-label parallel study in two phases. During phase 1, patients were screened and placed on maintena...
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/BF00877419
更新日期:1994-08-01 00:00:00
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
更新日期:2004-01-01 00:00:00
abstract::Cardiac reperfusion injury after heart transplantation or cardiopulmonary bypass has been difficult to control due to the variable degree of myocardial damage with respect to the length of ischemia and the complexity of the surgical procedure. Here, we evaluated the myocardial metabolic and functional recovery of hear...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF03029747
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::The results of the European Working Party for Hypertension in the Elderly Study showed that treatment of high blood pressure reduced the morbidity and mortality from strokes and myocardial infarction and reduced the incidence of heart failure in elderly patients. The largest number of hypertensive patients are elderly...
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/BF00053441
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Single- and multiple-dose studies were conducted to assess the pharmacokinetics, pharmacodynamics and safety of tolvaptan in healthy Japanese subjects. METHODS:All studies were single-center, randomized, placebo-controlled, single-blind or double-blind. In an ascending single-dose study, subjects were given 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/s10557-011-6299-3
更新日期:2011-12-01 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:PURPOSE:This study tested if the protective anti-remodeling effect of GLP-1 agonist Exendin-4 after an acute myocardial infarction (MI) in rats involves inhibition of the Wnt1/β-catenin signaling pathway. METHODS:Rats were divided into sham, sham + Exendin-4 (10 μg/day, i.p), MI, and MI + Exendin-4. MI was introduced ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-020-07006-9
更新日期:2020-05-30 00:00:00
abstract:PURPOSE:Epidemiologic and clinical research suggests important gender-related differences in the prevalence, presentation, associated conventional and non-conventional risk factors, management and outcomes of coronary heart disease (CHD) patients. Adequate data is not available for Indian population where prevalence of...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/s10557-015-6594-5
更新日期:2015-08-01 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::Left ventricular dysfunction is in most cases the consequence of myocardial ischemia. It may occur transiently during an attack of angina and usually it is reversible. It may persist over hours or even days in patients after an episode of ischemia followed by reperfusion, leading to the so-called condition of stunning...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF00877322
更新日期:1994-05-01 00:00:00
abstract::High-density lipoprotein cholesterol (HDL-c) has long been referred to as 'good cholesterol' due to its apparent inverse relationship with future CVD risk. More recent research has questioned a causal role for HDL-c in this relationship, however, as both genetic studies and numerous large-scale randomised controlled t...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/s10557-018-06846-w
更新日期:2019-04-01 00:00:00
abstract::The use of calcium antagonists and diuretics in combination for treatment of hypertension is controversial. In a single-blind study 16 patients (8 men, 8 women, age range 39 to 62 years) with primary hypertension of mild to moderate degree were given slow-release nifedipine 20 mg twice daily for 6 weeks, thereafter ei...
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/BF02125751
更新日期:1988-03-01 00:00:00
abstract::Annual mortality from congestive heart failure ranges from 15% to 60%, depending on the severity of the left ventricular damage and underlying disease. Most controlled trials have been too small to detect any beneficial effect on survival from the newer vasodilator and inotropic drugs. However, the results of two rece...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:
更新日期:1988-11-01 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::Free radical injury may contribute to the delayed postoperative recovery of myocardial metabolism and ventricular function after elective coronary artery revascularization. This clinical study was designed to evaluate, in stable angina patients having aortocoronary bypass surgery, whether orally administered alpha-toc...
journal_title:Cardiovascular drugs and therapy
pub_type: 临床试验,杂志文章
doi:10.1007/BF00054753
更新日期:1991-03-01 00:00:00
abstract::Patients with mild to moderate hypertension (diastolic blood pressure > or = 95 and < or = 115 mmHg) and renal dysfunction entered one of two studies to assess the safety of efficacious daily doses of quinapril on renal function and blood pressure. Twenty-four patients with moderate renal impairment (MRI) (creatinine ...
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/BF00877336
更新日期:1994-04-01 00:00:00
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
更新日期:1997-03-01 00:00:00
abstract::Although torsades de pointes is not a tightly demarcated entity, the diagnosis has important clinical implications. The concept should be retained. ...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章
doi:10.1007/BF03029821
更新日期:1991-02-01 00:00:00
abstract::Torsades de pointes (TdP) is a life-threatening ventricular tachycardia that occurs in the setting of a prolonged QT interval and is most frequently related to administration of antiarrhythmic drugs. Patients with organic heart disease, with low serum electrolyte levels, with a previous episode of TdP and with bradyca...
journal_title:Cardiovascular drugs and therapy
pub_type: 杂志文章,评审
doi:10.1007/BF03029778
更新日期:1991-04-01 00:00:00