Identification of patient subtypes based on protein expression for prediction of heart failure after myocardial infarction.

This study investigates the ability of high-throughput aptamer-based platform to identify circulating biomarkers able to predict occurrence of heart failure (HF), in blood samples collected during hospitalization of patients suffering from a first myocardial infarction (MI). REVE-1 (derivation) and REVE-2 (validation) cohorts included respectively 254 and 238 patients, followed up respectively 9 · 2 ± 4 · 8 and 7 · 6 ± 3 · 0 years. A blood sample collected during hospitalization was used for quantifying 4,668 proteins. Fifty proteins were significantly associated with long-term occurrence of HF with all-cause death as the competing event. k-means, an unsupervised clustering method, identified two groups of patients based on expression levels of the 50 proteins. Group 2 was significantly associated with a higher risk of HF in both cohorts. These results showed that a subset of 50 selected proteins quantified during hospitalization of MI patients is able to stratify and predict the long-term occurrence of HF.

Mitochondrial-Targeted Therapies Require Mitophagy to Prevent Oxidative Stress Induced by SOD2 Inactivation in Hypertrophied Cardiomyocytes.

Heart failure, mostly associated with cardiac hypertrophy, is a major cause of illness and death. Oxidative stress causes accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction, suggesting that mitochondria-targeted therapies could be effective in this context. The purpose of this work was to determine whether mitochondria-targeted therapies could improve cardiac hypertrophy induced by mitochondrial ROS. We used neonatal (NCMs) and adult (ACMs) rat cardiomyocytes hypertrophied by isoproterenol (Iso) to induce mitochondrial ROS. A decreased interaction between sirtuin 3 and superoxide dismutase 2 (SOD2) induced SOD2 acetylation on lysine 68 and inactivation, leading to mitochondrial oxidative stress and dysfunction and hypertrophy after 24 h of Iso treatment. To counteract these mechanisms, we evaluated the impact of the mitochondria-targeted antioxidant mitoquinone (MitoQ). MitoQ decreased mitochondrial ROS and hypertrophy in Iso-treated NCMs and ACMs but altered mitochondrial structure and function by decreasing mitochondrial respiration and mitophagy. The same decrease in mitophagy was found in human cardiomyocytes but not in fibroblasts, suggesting a cardiomyocyte-specific deleterious effect of MitoQ. Our data showed the importance of mitochondrial oxidative stress in the development of cardiomyocyte hypertrophy. We observed that targeting mitochondria by MitoQ in cardiomyocytes impaired the metabolism through defective mitophagy, leading to accumulation of deficient mitochondria.