The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice.

Heart failure (HF) and atrial fibrillation (AF) share common risk factors, frequently coexist and are associated with high mortality. Treatment of HF with AF represents a major unmet need. Here we show that a small molecule, BGP-15, improves cardiac function and reduces arrhythmic episodes in two independent mouse models, which progressively develop HF and AF.

Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies.

Cardiac hypertrophy can be defined as an increase in heart mass. Pathological cardiac hypertrophy (heart growth that occurs in settings of disease, e.g.

Protein kinase C promotes restoration of calcium homeostasis to platelet activating factor-stimulated human neutrophils by inhibition of phospholipase C.

Background: The role of protein kinase C (PKC) in regulating the activity of phospholipase C (PLC) in neutrophils activated with the chemoattractant, platelet-activating factor (PAF, 20 and 200 nM), was probed in the current study using the selective PKC inhibitors, GF10903X (0.5 - 1 muM) and staurosporine (400 nM).

Methods: Alterations in cytosolic Ca2+, Ca2+ influx, inositol triphosphate (IP3), and leukotriene B4 production were measured using spectrofluorimetric, radiometric and competitive binding radioreceptor and immunoassay procedures, respectively.

Reduced phosphoinositide 3-kinase (p110alpha) activation increases the susceptibility to atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia presenting at cardiology departments. A limited understanding of the molecular mechanisms responsible for the development of AF has hindered treatment strategies. The purpose of this study was to assess whether reduced activation of phosphoinositide 3-kinase (PI3K, p110alpha) makes the compromised heart susceptible to AF.

Role of phosphoinositide 3-kinases in regulating cardiac function.

Phosphoinositide 3-kinases (PI3Ks) are important signaling proteins in the heart. Class IA PI3Ks (p110alpha, beta) are critical regulators of physiological heart growth and cell survival, and are generally considered to be beneficial for heart function. In contrast, activation of class IB PI3K(p110gamma) is detrimental for heart function, reducing cardiac contractility.

The protective effects of exercise and phosphoinositide 3-kinase (p110alpha) in the failing heart.

Despite the development of a wide range of therapies, heart failure remains a leading cause of death in Western society. New therapies are needed to help combat this debilitating condition. Exercise is becoming an increasingly important feature of rehabilitation programmes for patients with heart failure.

Promoting physiological hypertrophy in the failing heart.

1. Heart failure rates have reached epidemic proportions in Western society. 2.