Abstract 260: Adverse Transverse-Tubule Remodeling in a Rat Model of Heart Failure is Attenuated by Triiodothyronine (T3) Treatment

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

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Impairment of endothelium dependent responses in a rat model of chronic heart failure: effects of an exercise training protocol

Cardiovascular Research ◽

10.1093/cvr/26.7.694 ◽

1992 ◽

Vol 26 (7) ◽

pp. 694-697 ◽

Cited By ~ 35

Author(s):

D C Lindsay ◽

C Jiang ◽

F Brunotte ◽

S Adamopoulos ◽

A J S Coats ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Exercise Training ◽

Rat Model ◽

Training Protocol

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A novel tankyrase small-molecule inhibitor blocks canonical Wnt/β-catenin pathway and prevents heart failure in a rat model of myocardial infarction: A multimodal study

Vascular Pharmacology ◽

10.1016/j.vph.2015.11.049 ◽

2015 ◽

Vol 75 ◽

pp. 61

Author(s):

M. Matteucci ◽

V. Casieri ◽

K. Gabisonia ◽

G.D. Aquaro ◽

G. Pollio ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Small Molecule ◽

Rat Model ◽

Small Molecule Inhibitor ◽

Molecule Inhibitor ◽

Canonical Wnt

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Use of genechips to analyse gene expression patterns in a rat model of ischemic heart failure

Journal of Molecular and Cellular Cardiology ◽

10.1016/s0022-2828(02)90813-8 ◽

2002 ◽

Vol 34 (6) ◽

pp. A22

Author(s):

Barbara Fellner ◽

Karola Trescher ◽

Severin Semsroth ◽

Karin Hoffmann-Sommergruber ◽

Wolfgang Schmidt ◽

...

Keyword(s):

Gene Expression ◽

Heart Failure ◽

Rat Model ◽

Expression Patterns ◽

Ischemic Heart ◽

Gene Expression Patterns ◽

Ischemic Heart Failure

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Abstract 13810: TT-00920, a Clinical Stage Novel Phosphodiesterase 9 Inhibitor, Protects Against Heart Failure in a Rat Model of Myocardial Infarction

Circulation ◽

10.1161/circ.142.suppl_3.13810 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Zejuan Sheng ◽

Xiaoyan Qiang ◽

Guoyu Li ◽

Huimin Wang ◽

Wenxin Dong ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Cardiac Function ◽

Rat Model ◽

Cardiac Fibrosis ◽

Clinical Stage ◽

Left Ventricular ◽

Guanosine Monophosphate ◽

Therapeutic Effects ◽

Dependent Manner

Introduction: Phosphodiesterase 9 (PDE9) controls natriuretic-peptide-stimulated cyclic guanosine monophosphate in cardiac myocytes and is stongly upregulated in human heart failure, suggesting its potential as a promising therapeutic target in heart failure. Here we investigated the potential effects of TT-00920, a clinical stage novel and highly selective PDE9 inhibitor, on heart failure in a rat model of myocardial infarction. Methods: Myocardial infarction was induced by left anterior descending coronary artery (LAD) ligation in male Sprague Dawley rats. After 4-week treatment of vehicle, LCZ696, TT-00920, or TT-00920/Valsartan by oral gavage, efficacy was assessed by echocardiography and cardiac histopathology. Results: TT-00920 had remarkably improved cardiac function, protected against cardiac remodeling and fibrosis in a dose-dependent manner. TT-00920/Valsartan combination showed superior beneficial efficacy when compared to TT-00920 or LCZ696 single agent.Figure 1. TT-00920 improved cardiac function and ventricular remodeling.Figure 2. TT-00920 attenuated cardiac fibrosis in peri-infarct zone. Conclusions: TT-00920 reversed LAD-induced left ventricular dysfunction and remodeling, supporting its potential as a novel therapeutic agent for heart failure. The superior efficacy of TT-00920/Valsartan combination suggests that TT-00920 and renin-angiotensin-aldosterone system inhibitors may have additive therapeutic effects in heart failure.TT-00920 is currently being evaluated in Phase 1 clinical study for safety, tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers (NCT04364789).

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