Oxidative stress refers to elevated intracellular levels of reactive oxygen species (ROS) that cause damage to lipids, proteins and DNA. Oxidative stress has been linked to a myriad of pathologies. However, elevated ROS are also signaling molecules i.e. redox biology that maintain physiological functions. In this review we discuss the two faces of ROS, redox signaling and oxidative stress, and their contribution to both physiological and pathological conditions. Redox biology refers to low levels of ROS that activate signaling pathways to initiate biological processes while oxidative stress denotes high levels of ROS that incur damage to DNA, protein or lipids. Thus, the response to ROS displays hormesis. The In this review, we argue that redox biology, rather than oxidative stress, underlies physiological and pathological conditions.

on behalf of the Telemedical Interventional Monitoring in Heart Failure InvestigatorsBackground-This study was designed to determine whether physician-led remote telemedical management (RTM) compared with usual care would result in reduced mortality in ambulatory patients with chronic heart failure (HF). Methods and Results-We enrolled 710 stable chronic HF patients in New York Heart Association functional class II or III with a left ventricular ejection fraction Յ35% and a history of HF decompensation within the previous 2 years or with a left ventricular ejection fraction Յ25%. Patients were randomly assigned (1:1) to RTM or usual care. Remote telemedical management used portable devices for ECG, blood pressure, and body weight measurements connected to a personal digital assistant that sent automated encrypted transmission via cell phones to the telemedical centers. The primary end point was death from any cause. The first secondary end point was a composite of cardiovascular death and hospitalization for HF. Baseline characteristics were similar between the RTM (nϭ354) and control (nϭ356)

Mitochondrial metabolism is necessary for the maintenance of oxidative TCA cycle function and mitochondrial membrane potential. Previous attempts to decipher whether mitochondria are necessary for biological outcomes have been hampered by genetic and pharmacologic methods that simultaneously disrupt multiple functions linked to mitochondrial metabolism. Here, we report that inducible depletion of mitochondrial DNA (ρ° cells) diminished respiration, oxidative TCA cycle function and the mitochondrial membrane potential resulting in diminished cell proliferation, hypoxic activation of HIF-1, and specific histone acetylation marks. Genetic reconstitution only of the oxidative TCA cycle function specifically in these inducible ρ° cells restored metabolites resulting in reestablishment of histone acetylation. In contrast, genetic reconstitution of the mitochondrial membrane potential restored ROS, which were necessary for hypoxic activation of HIF-1 and cell proliferation. These results indicate that distinct mitochondrial functions associated with respiration are necessary for cell proliferation, epigenetics, and HIF-1 activation.

Background-Endomyocardial biopsy (EMB) represents the gold standard for diagnosing myocarditis and nonischemic cardiomyopathies. This study focuses on the risk of complications and the respective diagnostic performance of left ventricular (LV), right ventricular (RV), or biventricular EMB in patients with suspected myocarditis and/or cardiomyopathy of unknown origin. Methods and Results-In this 2-center study, 755 patients with clinically suspected myocarditis (nϭ481) and/or cardiomyopathy of nonischemic origin including those with infiltrative or connective tissue disease (nϭ274) underwent either selective LV-EMB (nϭ265; 35.1%), selective RV-EMB (nϭ133; 17.6%), or biventricular EMB (nϭ357; 47.3%) after coronary angiography and exclusion of significant coronary artery disease. Cardiovascular magnetic resonance, including late gadolinium enhancement, imaging was performed in 540 patients (71.5%). The major complication rate for LV-EMB was 0.64% and for RV-EMB, 0.82%. Considering postprocedural pericardial effusion that occurred after biventricular EMB, the minor complication rate for LV-EMB varied between 0.64% to 2.89% and for RV-EMB, between 2.24% and 5.10%. Diagnostic EMB results were achieved significantly more often in those patients who underwent biventricular EMBs (79.3%) compared to those who underwent either selective LV-EMB or selective RV-EMB (67.3%; PϽ0.001). In patients with biventricular EMB, myocarditis was diagnosed in LV-EMB samples in 18.7% and in RV-EMB samples in 7.9% (Pϭ0.002) , and it was diagnosed in both ventricles in 73.4%. There were no differences in the number of positive LV-EMB, RV-EMB, or LV-and RV-EMB findings when related to the site of cardiovascular magnetic resonance-based late gadolinium enhancement. Conclusions-Both