A5091460776- Cardiac Ischemia and Reperfusion
- Chemotherapy-induced cardiotoxicity and mitigation
- Mitochondrial Function and Pathology
- Cardiac Imaging and Diagnostics
- Polymer Nanocomposite Synthesis and Irradiation
- Lanthanide and Transition Metal Complexes
- Muscle Physiology and Disorders
- GDF15 and Related Biomarkers
- Cardiac Fibrosis and Remodeling
- Electron Spin Resonance Studies
- Nutrition and Health in Aging
- Acute Myocardial Infarction Research
- Adipose Tissue and Metabolism
- Cancer, Hypoxia, and Metabolism
- Cardiac electrophysiology and arrhythmias
- Transplantation: Methods and Outcomes
- Metabolism and Genetic Disorders
- Diabetic Foot Ulcer Assessment and Management
- Traditional Chinese Medicine Analysis
- Wound Healing and Treatments
- Acute Ischemic Stroke Management
- Cancer Treatment and Pharmacology
- Anesthesia and Neurotoxicity Research
- Antiplatelet Therapy and Cardiovascular Diseases
- Cardiovascular Effects of Exercise
Spanish National Centre for Cardiovascular Research
2014-2024
Hospital Universitario Fundación Jiménez Díaz
2022
Centro de Investigación en Red en Enfermedades Cardiovasculares
2020-2021
Centro de Investigación Biomédica en Red
2020-2021
Anthracycline-induced cardiotoxicity is a major clinical problem, and early markers are needed. The purpose of this study was to identify doxorubicin-induced by serial multiparametric cardiac magnetic resonance (CMR) its pathological correlates in large animal model. Twenty pigs were included. Of these, 5 received biweekly intracoronary doxorubicin doses (0.45 mg/kg/injection) followed until sacrifice at 16 weeks. Another 3 A third group sacrificed after the dose. All groups underwent weekly...
Abstract The β1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size in acute myocardial infarction (AMI) patients. prevailing view has been that acts mainly on cardiomyocytes. Here, we demonstrate reperfusion injury by targeting the haematopoietic compartment. Metoprolol inhibits neutrophil migration an ADRB1-dependent manner. during early phases of recruitment impairing structural and functional rearrangements needed for productive engagement circulating platelets,...
Abstract Aims Clinical guidelines recommend early intravenous β-blockers during ongoing myocardial infarction; however, it is unknown whether all exert a similar cardioprotective effect. We experimentally compared three clinically approved β-blockers. Methods and results Mice undergoing 45 min/24 h ischaemia–reperfusion (I/R) received vehicle, metoprolol, atenolol, or propranolol at min 35. The effect on neutrophil infiltration was tested in models of exacerbated inflammation. Neutrophil...
Anthracycline-induced cardiotoxicity (AIC) debilitates quality of life in cancer survivors. Serial characterizations are lacking the molecular processes occurring with AIC. The aim this study was to characterize AIC progression a mouse model from early (subclinical) advanced heart failure stages, an emphasis on cardiac metabolism and mitochondrial structure function. CD1 mice received 5 weekly intraperitoneal doxorubicin injections (5 mg/kg) were followed by serial echocardiography for 15...
Abstract Aims The aim of this study was to changes in coronary microcirculation status during and after several cycles anthracycline treatment. Methods results Large-white male pigs (n=40) were included different experimental protocols (ExPr.) according cumulative exposure [0.45 mg/kg intracoronary (IC) doxorubicin per injection] follow-up: control (no doxorubicin); single injection sacrifice either at 48 h (ExPr. 1) or 2 weeks 2); 3 injections apart (low dose) 3) 12 4) third injection; five...
Abstract Aims Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. Methods and results Forty Large-White pigs were included. In Study 1, 20 randomized 1:1 remote ischaemic preconditioning (RIPC, 3 cycles 5 min leg ischaemia followed by reperfusion) or pretreatment. RIPC was performed immediately before...
Abstract Aims Heart failure and associated cachexia is an unresolved important problem. This study aimed to determine the factors that contribute cardiac in a new model of heart mice lack integrated stress response (ISR) induced eIF2α phosphatase, PPP1R15A. Methods results Mice were irradiated reconstituted with bone marrow cells. lacking functional PPP1R15A, exhibited dilated cardiomyopathy severe weight loss following irradiation, whilst wild-type unaffected. was increased expression Gdf15...
Abstract Aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and heart failure (HF). There a lack of therapies able to prevent/revert AS-induced HF. Beta3 adrenergic receptor (β3AR) signaling beneficial in several forms Here, we studied the potential effect β3AR overexpression on Selective stimulation had positive inotropic effect. Transgenic mice constitutively overexpressing human (c-hβ3tg) were protected from development HF response induced AS, against cardiomyocyte...
β3-Adrenergic receptor (β3AR) agonists have been shown to protect against ischemia-reperfusion injury (IRI). Since β3ARs are present both in cardiomyocytes and endothelial cells, the cellular compartment responsible for this protection has remained unknown. Using transgenic mice constitutively expressing human β3AR (hβ3AR) or endothelium on a genetic background of null endogenous expression, we show that only cardiomyocyte expression protects IRI (45 min ischemia followed by reperfusion over...
Introduction: Early intravenous administration of metoprolol has been shown to reduce infarct size and improve long-term cardiac function in the randomized clinical trial METOCARD-CNIC led by our group. However, mechanisms underlying its favorable benefits remain unclear. PSGL1-dependent neutrophil-platelet interactions have critical implications on microvascular obstruction neutrophil infiltration both which determine extent size. We hypothesized that before reperfusion blocks formation...
Aims: Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect in significant proportion of cancer patients. A central mechanism AIC irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. Methods and Results: Forty Large-White pigs were included. In Study 1, 20 randomized 1:1 remote ischemic pre-conditioning (RIPC, 3 cycles 5 min leg ischemia followed by reperfusion) or pretreatment. RIPC was performed...
Abstract Heart failure and associated cachexia is an unresolved important problem. We report a new model of severe heart that consistently results in cachexia. Mice lacking the integrated stress response (ISR) induced eIF2α phosphatase, PPP1R15A, exhibit dilated cardiomyopathy weight loss following irradiation, whilst wildtype mice are unaffected. This with increased expression Gdf15 levels GDF15 circulation. provide evidence blockade activity prevents slows progression failure. Our data...
Background: Beta3-adrenergic receptor (b3AR) stimulation reduces myocardial ischemia/reperfusion injury (IRI) in vivo. The aim of this study was to assess whether effect is exerted directly the cardiomyocytes and investigate role mPTP protection.
Abstract Background Despite the increased effectiveness of chemotherapeutic agents, cancer represents a lethal illness worldwide and anticancer strategies still present severe adverse effects. Cardiac dysfunction is dose-dependent common affliction anthracyclines treatment. Anthracycline-induced cardiotoxicity (AIC) consequent heart failure has recently been suggested to be mediated by mitochondrial dysfunction; however, molecular mechanisms driving this connection are incompletely...
Abstract Background/Introduction Dilated cardiomyopathy (DCM) is a leading cause of heart failure (HF) in young and middle aged individuals worldwide. Alterations mitochondrial dynamics (fusion/fission) quality control (mitophagy) are critical for normal cardiac function. Imbalanced towards fission has been shown to contribute DCM development mice with ablation the protease YME1L, which results altered OPA1 processing precluding fusion. In these mice, phenotype includes metabolic...
Abstract Background/Introduction Cardiotoxicity (CT) is a major concern for cancer patients receiving anthracyclines. While the effect of anthracyclines on cardiomyocytes well established, its impact myocardial microcirculation has not been characterized. Purpose To evaluate low and high cumulative doses doxorubicin (doxo) anatomical functional vasculature status evaluated by serial invasive Coronary Flow Reserve (CFR) Cardiac Magnetic Resonance (CMR)-based quantitative perfusion in large...
Abstract Introduction Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect occurring in significant proportion of patients. Irreversible mitochondrial damage central mechanism AIC. Despite many efforts, there lack therapies able to prevent Remote ischemic preconditioning (RIPC) could be promising therapy AIC due the scheduled application chemotherapy cancer Purpose To evaluate cardioprotective efficacy RIPC large animal model Methods Large-White pigs (n=20) underwent...