465 Beta-2 adrenergic receptors polymorphisms influence the effects of carvedilol in the patients with chronic heart failure

2007 ◽  
Vol 6 (1) ◽  
pp. 100-100
Author(s):  
M METRA ◽  
S NODARI ◽  
N PEZZALI ◽  
L COVOLO ◽  
G ORIZIO ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Adrenergic Receptors ◽  
Beta 2

Abstract 11087: Autoantibody Titer Directed Against β1-Adrenergic Receptors is a Predictor of Reverse Remodeling During Carvedilol Therapy for Chronic Heart Failure: Japanese Chronic Heart Failure (J-CHF) Study

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yuji Nagatomo ◽  
Tsutomu Yoshikawa ◽  
Hiroshi Okamoto ◽  
Akira Kitabatake ◽  
Masatsugu Hori ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Adrenergic Receptors ◽  
High Titer ◽  
Left Ventricular ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Left Ventricular Ejection ◽  
Reverse Remodeling ◽  
Ventricular Ejection Fraction ◽  
Lv Volume

Introduction: Autoimmune disorder is one of the features characterizing congestive heart failure (CHF) not only due to idiopathic dilated cardiomyopathy, but due to other etiologies. Autoantibody directed against β1-adrenergic receptors (β1-AAb) exerts agonist-like action inducing receptor uncoupling, and elicits persistent myocardial damage. We, therefore, attempted to determine the significance of β1-AAb in patients with CHF who received β-blocker carvedilol in the substudy of J-CHF study. Methods: In this prospective, randomized, multicenter trial, 117 patients (left ventricular ejection fraction [LVEF] ≤ 40%) with mild to moderate CHF were assigned to 2.5mg/5mg/20mg (n=38/36/43) carvedilol groups according to the target dose. Sera were collected at baseline and β1-AAb titer was determined using ELISA. Results: ELISA showed 66 patients as negative and 36/7/7/1 patients as 20-fold (x20) / x40 / x80 / x160 positive, respectively. When the study population was divided into β1-AAb high titer (≥ x40, H) and low titer (≤ x20, L) groups, there were no significant differences in vital signs or cardiac function at baseline between 2 groups. The % change of LVEF during 56 weeks after carvedilol introduction (ΔLVEF) was significantly larger in H than L (H, +85±78% vs. L, +43±65%, p=0.04). LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) decreased to a greater extent in H than L during 56 weeks (LVEDV, 182±50 to 119±43 ml vs. 202±52 to 167±58 ml, p<0.005 by ANOVA; LVESV, 136±47 to 62±36 ml vs. 141±47 to 97±53 ml, p=0.048 by ANOVA). β1-AAb titer was significantly correlated with ΔLVEF and the % change of LV volume (LVEF, r=0.24, p=0.02; LVEDV, r=-0.26, p=0.02; LVESV r=-0.27, p=0.01). Multiple regression analysis demonstrated that β1-AAb titer was an independent predictor of ΔLVEF and the % changes of LV volume after adjusting for age, gender, allocated dose of carvedilol, heart rate at baseline, plasma BNP at baseline, etiology of CHF and the presence of atrial fibrillation (ΔLVEF β=0.286, p=0.01; ΔLVEDV β=-0.227, p=0.04; ΔLVESV, β=-0.250, p=0.02). Conclusions: The findings in the present study suggested that β1-AAb has a crucial role as one of the determinants of reverse remodeling during carvedilol therapy for patients with CHF.

scholarly journals Autoantibodies Activating Human β 1 -Adrenergic Receptors Are Associated With Reduced Cardiac Function in Chronic Heart Failure

Circulation ◽  
1999 ◽  
Vol 99 (5) ◽  
pp. 649-654 ◽  
Author(s):  
Roland Jahns ◽  
Valérie Boivin ◽  
Christian Siegmund ◽  
Gerhard Inselmann ◽  
Martin J. Lohse ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Function ◽  
Adrenergic Receptors

Higenamine, a Dual Agonist for β 1- and β 2-Adrenergic Receptors Identified by Screening a Traditional Chinese Medicine Library

Planta Medica ◽  
2019 ◽  
Vol 85 (09/10) ◽  
pp. 738-744 ◽  
Author(s):  
Yanmin Chen ◽  
Bujing Guo ◽  
Hongda Zhang ◽  
Lihong Hu ◽  
Jue Wang
Keyword(s):  
Heart Failure ◽  
Chinese Medicine ◽  
Chronic Heart Failure ◽  
Traditional Chinese Medicine ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Receptor Signaling ◽  
Heart Failure Treatment ◽  
Failure Treatment ◽  
Dual Agonist

AbstractChronic heart failure is the terminal stage of various cardiovascular diseases. Despite the availability of several classes of drugs, there is still an unmet need for effective treatment. Based on bench work during the past two decades, we have proposed that enhancement of β 2-adrenergic receptor signaling in combination with the presently preferred β 1-adrenergic receptor blockade would be a promising strategy. Chinese herbal medicines have been shown to be effective in the treatment of heart failure, although the mechanisms largely remain unknown. In the present study, we screened an herbal medicine compound/extract library for β-adrenergic receptor ligands to determine the target of certain effective botanical remedies and seek a leading compound(s) for chronic heart failure treatment. Using a high-throughput screening assay, we identified higenamine, which has a long history in chronic heart failure treatment in traditional Chinese medicine, to be a potent β-adrenergic receptor agonist. Further experiments using specific inhibitors showed that higenamine activated both β 1-adrenergic receptor and β 2-adrenergic receptor. Inhibition of its action by pertussis toxin (a Gi inhibitor) indicated that it is a β 2-adrenergic receptor Gs/Gi dual agonist. Contractility experiments demonstrated a positive inotropic effect of higenamine. In conclusion, we found an herbal compound, higenamine, to be a dual agonist for β 1/β 2-adrenergic receptors with no preference in stimulating the Gs and Gi pathways in β 2-adrenergic receptor signaling. Our results elucidated not only the target of higenamine to explain its pharmacological effect in treating chronic heart failure, but also the mechanisms of its cardiac toxicity.

Sign in / Sign up

Export Citation Format

Share Document