GDF15 antagonism limits severe heart failure and prevents cardiac cachexia.

Aims: Heart failure and associated cachexia is an unresolved and important problem. This study aimed to determine the factors that contribute to cardiac cachexia in a new model of heart failure in mice that lack the integrated stress response (ISR) induced eIF2α phosphatase, PPP1R15A.

Methods And Results: Mice were irradiated and reconstituted with bone marrow cells.

β3-Adrenergic receptor overexpression in cardiomyocytes preconditions mitochondria to withstand ischemia-reperfusion injury.

β3-Adrenergic receptor (β3AR) agonists have been shown to protect against ischemia-reperfusion injury (IRI). Since β3ARs are present both in cardiomyocytes and in endothelial cells, the cellular compartment responsible for this protection has remained unknown. Using transgenic mice constitutively expressing the human β3AR (hβ3AR) in cardiomyocytes or in the endothelium on a genetic background of null endogenous β3AR expression, we show that only cardiomyocyte expression protects against IRI (45 min ischemia followed by reperfusion over 24 h).

Anthracycline Cardiotoxicity Induces Progressive Changes in Myocardial Metabolism and Mitochondrial Quality Control: Novel Therapeutic Target.

Background: Anthracycline-induced cardiotoxicity (AIC) debilitates quality of life in cancer survivors. Serial characterizations are lacking of the molecular processes occurring with AIC.

Objectives: The aim of this study was to characterize AIC progression in a mouse model from early (subclinical) to advanced heart failure stages, with an emphasis on cardiac metabolism and mitochondrial structure and function.

Beta-3 adrenergic receptor overexpression reverses aortic stenosis-induced heart failure and restores balanced mitochondrial dynamics.

Aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and heart failure (HF). There is a lack of therapies able to prevent/revert AS-induced HF. Beta3 adrenergic receptor (β3AR) signaling is beneficial in several forms of HF.

Coronary microcirculation damage in anthracycline cardiotoxicity.

Aims: The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment.

Methods And Results: Large-white male pigs (n=40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure [0.

Metoprolol exerts a non-class effect against ischaemia-reperfusion injury by abrogating exacerbated inflammation.

Aims: Clinical guidelines recommend early intravenous β-blockers during ongoing myocardial infarction; however, it is unknown whether all β-blockers exert a similar cardioprotective effect. We experimentally compared three clinically approved intravenous β-blockers.

Methods And Results: Mice undergoing 45 min/24 h ischaemia-reperfusion (I/R) received vehicle, metoprolol, atenolol, or propranolol at min 35.

Remote ischaemic preconditioning ameliorates anthracycline-induced cardiotoxicity and preserves mitochondrial integrity.

Aims: Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC.

Translational large animal model of hibernating myocardium: characterization by serial multimodal imaging.

Nonrevascularizable coronary artery disease is a frequent cause of hibernating myocardium leading to heart failure (HF). Currently, there is a paucity of therapeutic options for patients with this condition. There is a lack of animal models resembling clinical features of hibernating myocardium.

Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity.

Background: Anthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed.

Objectives: The purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological correlates in a large animal model.

Methods: Twenty pigs were included.

Neutrophil stunning by metoprolol reduces infarct size.

The β1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size in acute myocardial infarction (AMI) patients. The prevailing view has been that metoprolol acts mainly on cardiomyocytes. Here, we demonstrate that metoprolol reduces reperfusion injury by targeting the haematopoietic compartment.