Glucagon Receptor Antagonism Ameliorates Progression of Heart Failure.

Mice were treated with a fully human monoclonal glucagon receptor antagonistic antibody REMD2.59 following myocardial infarction or pressure overload. REMD2.59 treatment blunted cardiac hypertrophy and fibrotic remodeling, and attenuated contractile dysfunction at 4 weeks after myocardial infarction. In addition, REMD2.59 treatment at the onset of pressure overload significantly suppressed cardiac hypertrophy and chamber dilation with marked preservation of cardiac systolic and diastolic function. Initiation of REMD2.59 treatment 2 weeks after pressure overload significantly blunted the progression of cardiac pathology. These results provide the first in vivo proof-of-concept evidence that glucagon receptor antagonism is a potentially efficacious therapy to ameliorate both onset and progression of heart failure

Irisin Lowers Blood Pressure by Improvement of Endothelial Dysfunction via AMPK‐Akt‐eNOS‐NO Pathway in the Spontaneously Hypertensive Rat

Background Exercise is a major nonpharmacological treatment for hypertension, but its underlying mechanisms are still not completely elucidated. Irisin, a polypeptide containing 112 amino acids, which is secreted mainly by skeletal muscle cells during exercise, exerts a protective role in metabolic diseases, such as diabetes mellitus and obesity. Because of the close relationship between irisin and metabolic diseases, we hypothesized that irisin may play a role in the regulation of blood pressure. Methods and Results Blood pressures of male Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were monitored through the carotid artery. Our study found that acute intravenous injection of irisin reduced blood pressure in SHRs, but not WKY rats. Irisin, by itself, had no direct vasorelaxing effect in phenylephrine‐preconstricted mesenteric arteries from SHRs. However, irisin augmented the acetylcholine‐induced vasorelaxation in mesenteric arteries from SHRs that could be reversed by Nω‐nitro‐L‐arginine‐methyl ester (L‐NAME;100 μmol/L), indicating a role of nitric oxide (NO) in this action. Indeed, irisin increased NO production and phosphorylation of endothelial nirtic oxide synthase (eNOS) in endothelial cells. 5′‐AMP‐activated protein kinase (AMPK) was involved in the vasorelaxing effect of irisin because compound C (20 μmol/L), an AMPKinhibitor, blocked the irisin‐mediated increase in phosphorylation of eNOS and protein kinase B (Akt) in endothelial cells and vasodilation in mesenteric arteries. Conclusions We conclude that acute administration of irisin lowers blood pressure of SHRs by amelioration of endothelial dysfunction of the mesenteric artery through the AMPK‐Akt‐eNOS‐NO signaling pathway

Radiofrequency ablation can reverse the structural remodeling caused by frequent premature ventricular contractions originating from the right ventricular outflow tract even in a normal heart

OBJECTIVE: The aim of this study was to evaluate whether frequent premature ventricular contractions originating from the right ventricular outflow tract remodel the cardiac structure and function in patients with a “seemingly normal heart” and whether radiofrequency ablation can reverse this remodeling. METHODS: Sixty-eight patients with idiopathic frequent premature ventricular contractions originating from the right ventricular outflow tract and normal heart structure and function were enrolled in this study. The patients were divided into three groups according to the therapeutic method: radiofrequency ablation group (24 cases), anti-arrhythmia drug group (26 cases), and control group (18 cases without any treatment). Clinical Registration number: ChiCTR-ONRC-12002834 RESULTS: The basic patient characteristics were comparable between the three groups, except for the premature ventricular contraction rate, which was significantly lower in the control group. After six months of follow up, the premature ventricular contraction rate was significantly reduced in the radiofrequency ablation group, which was accompanied by a significant decrease in the following cardiac cavity inner diameters, as determined by echocardiography: right atrium (33.33±3.78 vs. 30.05±2.60 mm, p = 0.001), right ventricle (23.24±2.40 vs. 21.05±2.16 mm, p = 0.020), and left ventricle (44.76±4.33 vs. 41.71±3.44 mm, p = 0.025). These results were similar in the anti-arrhythmia drug group, although this group exhibited a smaller extent of change (right atrium: 33.94±3.25 vs. 31.27±3.11 mm, p = 0.024; right ventricle: 22.97±3.09 vs. 21.64±2.33 mm, p = 0.049; left ventricle: 45.92±6.38 vs. 43.84±5.67 mm, p = 0.039), but not in the control group (p>;0.05). There was a tendency toward improvement in the cardiac functions in both the radiofrequency ablation and anti-arrhythmia drug groups. However, these differences were not statistically significant (p>;0.05). CONCLUSIONS: These results indicate that radiofrequency ablation can potentially reverse the cardiac remodeling caused by frequent premature ventricular contractions even in structurally normal hearts and that frequent premature ventricular contractions should be abated even in structurally normal hearts