Exercise Training Restores Cardiac Protein Quality Control in Heart Failure

Exercise training is a well-known coadjuvant in heart failure treatment; however, the molecular mechanisms underlying its beneficial effects remain elusive. Despite the primary cause, heart failure is often preceded by two distinct phenomena: mitochondria dysfunction and cytosolic protein quality control disruption. The objective of the study was to determine the contribution of exercise training in regulating cardiac mitochondria metabolism and cytosolic protein quality control in a post-myocardial infarction-induced heart failure (MI-HF) animal model. Our data demonstrated that isolated cardiac mitochondria from MI-HF rats displayed decreased oxygen consumption, reduced maximum calcium uptake and elevated H2O2 release. These changes were accompanied by exacerbated cardiac oxidative stress and proteasomal insufficiency. Declined proteasomal activity contributes to cardiac protein quality control disruption in our MI-HF model. Using cultured neonatal cardiomyocytes, we showed that either antimycin A or H2O2 resulted in inactivation of proteasomal peptidase activity, accumulation of oxidized proteins and cell death, recapitulating our in vivo model. Of interest, eight weeks of exercise training improved cardiac function, peak oxygen uptake and exercise tolerance in MI-HF rats. Moreover, exercise training restored mitochondrial oxygen consumption, increased Ca2+-induced permeability transition and reduced H2O2 release in MI-HF rats. These changes were followed by reduced oxidative stress and better cardiac protein quality control. Taken together, our findings uncover the potential contribution of mitochondrial dysfunction and cytosolic protein quality control disruption to heart failure and highlight the positive effects of exercise training in re-establishing cardiac mitochondrial physiology and protein quality control, reinforcing the importance of this intervention as a nonpharmacological tool for heart failure therapy.

Probabilistic failure modelling of reinforced concrete structures subjected to chloride penetration

Structural durability is an important criterion that must be evaluated for every type of structure. Concerning reinforced concrete members, chloride diffusion process is widely used to evaluate durability, especially when these structures are constructed in aggressive atmospheres. The chloride ingress triggers the corrosion of reinforcements; therefore, by modelling this phenomenon, the corrosion process can be better evaluated as well as the structural durability. The corrosion begins when a threshold level of chloride concentration is reached at the steel bars of reinforcements. Despite the robustness of several models proposed in literature, deterministic approaches fail to predict accurately the corrosion time initiation due the inherent randomness observed in this process. In this regard, structural durability can be more realistically represented using probabilistic approaches. This paper addresses the analyses of probabilistic corrosion time initiation in reinforced concrete structures exposed to chloride penetration. The chloride penetration is modelled using the Fick's diffusion law. This law simulates the chloride diffusion process considering time-dependent effects. The probability of failure is calculated using Monte Carlo simulation and the first order reliability method, with a direct coupling approach. Some examples are considered in order to study these phenomena. Moreover, a simplified method is proposed to determine optimal values for concrete cover.