Investigation into the Protective Effects of Hypaconitine and Glycyrrhetinic Acid Against Chronic Heart Failure of the Rats

Abstract BackgroundThe present study aimed to determine the protective effects of hypaconitine (HA) and glycyrrhetinic acid (GA) against chronic heart failure (CHF) in the rats and to explore the underlying molecular mechanisms.Methods The CHF rat model was established by transverse-aortic constriction (TAC) operation. The total cholesterol (TCHO) and triglyceride (TG) levels were determined by ELISA assay. The protein expression of fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) in the rat ventricular tissues was determined by immunohistochemistry. The serum metabolites were determined by LC-MS/MS assay.ResultsHA + GA treatment significantly reduced the plasma levels of TCHO and TG in the CHF rats. The expression of FGF2 and VEGFA protein was up-regulated and the expression of eNOS protein was down-regulated in the ventricular tissues of CHF rats, which was significantly restored after HA + GA treatment. HA + GA treatment down-regulated serum isonicotinic acid, phosphatidylcholine, cardiolipin, estrogen glucuronide, and glycocholic acid, up-regulated serum sphingosine and deoxycholic acid in the CHF rats.ConclusionIn conclusion, HA +GA showed protective effects on CHF in the rats, and the HA + GA may exert protective effects by reducing lipid levels, up-regulating the expression of FGF2 and VEGFA proteins, attenuating eNOS protein expression, and modulating metabolic pathways. However, the molecular mechanisms underlying HA + GA-mediated effects still require further examination.

Download Full-text

Low Insulin-like Growth factor-I Predicts Wasting, Anabolic Deficiency, Cytokine and Neurohormonal Activation in Chronic Heart Failure

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(97)84071-5 ◽

1998 ◽

Vol 31 (2) ◽

pp. 84A ◽

Cited By ~ 1

Author(s):

J Niebauer

Keyword(s):

Heart Failure ◽

Growth Factor ◽

Chronic Heart Failure ◽

Insulin Like Growth Factor ◽

Neurohormonal Activation ◽

Factor I ◽

Growth Factor I

Download Full-text

Plasma insulin-like growth factor I as predictor of progression and all cause mortality in chronic heart failure

Growth Hormone & IGF Research ◽

10.1016/j.ghir.2009.03.003 ◽

2009 ◽

Vol 19 (6) ◽

pp. 486-490 ◽

Cited By ~ 22

Author(s):

Mikkel Andreassen ◽

Caroline Kistorp ◽

Ilan Raymond ◽

Per Hildebrandt ◽

Finn Gustafsson ◽

...

Keyword(s):

Heart Failure ◽

Growth Factor ◽

Chronic Heart Failure ◽

Plasma Insulin ◽

Insulin Like Growth Factor ◽

Factor I ◽

All Cause Mortality ◽

Growth Factor I

Download Full-text

Omega-3 Polyunsaturated Fatty Acids in Chronic Heart Failure: Evidence of Atrial Protective Effects in an Ovine Model

Heart Lung and Circulation ◽

10.1016/j.hlc.2010.06.880 ◽

2010 ◽

Vol 19 ◽

pp. S91

Author(s):

D. Lau ◽

A. Carbone ◽

P. Psaltis ◽

D. Kelly ◽

L. Mackenzie ◽

...

Keyword(s):

Heart Failure ◽

Fatty Acids ◽

Chronic Heart Failure ◽

Polyunsaturated Fatty Acids ◽

Protective Effects ◽

Omega 3 ◽

Ovine Model

Download Full-text

Adenosine and Cardioprotection in Chronic Heart Failure: Genes and Protein Expression

Hypertension Research ◽

10.1291/hypres.30.757 ◽

2007 ◽

Vol 30 (9) ◽

pp. 757-758 ◽

Cited By ~ 3

Author(s):

Ichiro HISATOME

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Protein Expression

Download Full-text

Abstract 1236: A Molecular and Functional Basis for Focal Arrhythmogenesis in Heart Failure-associated Atrial Fibrillation

Circulation ◽

10.1161/circ.116.suppl_16.ii_251-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Yung-Hsin Yeh ◽

Reza Wakili ◽

Xiao Yan Qi ◽

Denis Chartier ◽

Stefan Kääb ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Protein Expression ◽

Action Potentials ◽

Molecular Mechanisms ◽

Potential Role ◽

Regulatory Proteins ◽

Related Protein ◽

Triggered Activity ◽

Delayed Afterdepolarizations

Introduction: Heart failure (HF) frequently causes atrial fibrillation (AF) and focal sources of unknown mechanism have been implicated. Here, we studied the potential role and molecular mechanisms of Ca 2+ handling abnormalities. Methods: Ca 2+ handling (microfluorescence, Indo-1 AM) and related protein expression (Western blot) were assessed in left atria of 20 dogs with ventricular tachypacing (240 bpm × 2 wks)-induced HF and 20 controls (CTLs). Whole-cell perforated-patch was used to record action potentials (APs), delayed afterdepolarizations (DADs) and triggered activity. Results : HF increased [Ca 2+ ] i transient amplitude from 239±24 to 444±43* nM (*P<0.05), and [Ca 2+ ] i release by 10 mM local caffeine puffs (an index of SR Ca 2+ content) from 849±71 (CTL) to 1574±169* nM (HF). Spontaneous Ca 2+ release events increased from 1.8±0.5 (CTL) to 10.7±2.1* events/run (HF). HF significantly increased APD (by ~40% at 1 Hz). DADs and triggered activity were more common in HF (15.2±2.6 triggered APs/run, vs CTL 0.4±0.2*), and were abolished by ryanodine (10 μM), but not by the I f -blocker Cs + (2 mM). HF caused profound changes in protein expression of key Ca 2+ handling and regulatory proteins (Table ). Calsequestrin, the major SR Ca 2+ -binding protein, was reduced by 32%*. Fractional RYR2 PKA (Ser2809) phosphorylation decreased by 63%*, whereas CaMKII (Ser2815) RYR2 phosphorylation increased by 221%*. The catalytic and regulatory (RII) PKA subunits were downregulated by 15%* and 73%*, whereas expression and autophosphorylation (Thr287) of CaMKIIδ were increased by 45%* and 81%* respectively. NCX1, SERCA and total, PKA and CaMKII phosphorylated SERCA-regulatory phospholamban were unchanged by HF. Conclusions: HF causes profound changes in regulation and expression of atrial Ca 2+ handling proteins, producing increased SR Ca 2+ load and release, along with DADs and triggered activity that may account for focal mechanisms that initiate and/or sustain HF-related AF.

Download Full-text