Aldosterone receptor antagonists in cardiovascular disease: a review of the recent literature and insight into potential future indications.

Randomized controlled trials demonstrate the efficacy of aldosterone receptor antagonists (spironolactone and eplerenone) as a useful pharmacologic intervention specifically in patients with New York Heart Association (NYHA) class III and IV heart failure, in patients with an ejection fraction <40% after myocardial infarction, and most recently in patients with mildly symptomatic heart failure. However, aldosterone receptor antagonists may be beneficial in a broader patient population. Aldosterone receptor antagonists can potentially serve as an antiarrhythmic pharmacologic agent for atrial and ventricular arrhythmias, an anti-ischemic medication in coronary artery disease through prevention of myocardial fibrosis and vascular damage, and as an agent in people with asymptomatic and mild heart failure (NYHA classes I and II) and diastolic heart failure. However, many clinicians remain reluctant to prescribe this highly efficacious pharmacologic therapy for a variety of reasons, including concerns about polypharmacy and hyperkalemia. Recent observational analysis demonstrates that less than one-third of eligible patients hospitalized with heart failure actually received aldosterone antagonist therapy. This article will review the current and potential future uses of aldosterone receptor antagonists across the entire spectrum of cardiovascular disease. The authors have no funding, financial relationships, or conflicts of interest to disclose.

APL-1, a Caenorhabditis elegans protein related to the human beta-amyloid precursor protein, is essential for viability.

Dominant mutations in the amyloid precursor protein (APP) gene are associated with rare cases of familial Alzheimer's disease; however, the normal functions of APP and related proteins remain unclear. The nematode Caenorhabditis elegans has a single APP-related gene, apl-1, that is expressed in multiple tissues. Loss of apl-1 disrupts several developmental processes, including molting and morphogenesis, and results in larval lethality. The apl-1 lethality can be rescued by neuronal expression of the extracellular domain of APL-1. These data highlight the importance of the extracellular domain of an APP family member and suggest that APL-1 acts noncell-autonomously during development. Overexpression of APL-1 also causes several defects, including a high level of larval lethality. Decreased activity of sel-12, a C. elegans homologue of the human gamma-secretase component presenilin 1, partially rescues the lethality associated with APL-1 overexpression, suggesting that SEL-12 activity regulates APL-1 activity either directly or indirectly.