The Role of Osteoprotegerin and Its Ligands in Vascular Function

International audience; The superfamily of tumor necrosis factor (TNF) receptors includes osteoprotegerin (OPG) and its ligands, which are receptor activators of nuclear factor kappa-B ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). The OPG/RANKL/RANK system plays an active role in pathological angiogenesis and inflammation as well as cell survival. It has been demonstrated that there is crosstalk between endothelial cells and osteoblasts during osteogenesis, thus establishing a connection between angiogenesis and osteogenesis. This OPG/RANKL/RANK/TRAIL system acts on specific cell surface receptors, which are then able to transmit their signals to other intracellular comp…

P4613Long-term impact of postnatal nutritional programming on cardiac sensitivity to ischemia-reperfusion injury in vivo and on cardio-protective pathways in mice

Abstract Introduction Nutritional disturbances during the postnatal period may be responsible for a predisposition, or “programming”, to increased cardio-metabolic risk and to a progressive alteration of left ventricular contractility in adulthood. This nutritional perinatal programming may also lead to an alteration of cellular pathways involved in cardiac protection, such as the specific RISK and SAFE pathways, highlighted during pre- and post-ischemic conditioning or those of sirtuins (SIRT), histone deacetylases involved in the regulation of essential biological process. Purpose Our aim was to evaluate in mice the impact of postnatal overfeeding (PNOF) on cardiac sensitivity to ischemia…

P1742Experimental ischemic stroke in rats induce myocardial contractile dysfunction in vivo and ex vivo and increase cardiac vulnerability to ischemia-reperfusion injury ex vivo

Role of humanin, a mitochondrial-derived peptide, in cardiovascular disorders

The mitochondria produce specific peptides-mitochondrial-derived peptides-that mediate the transcriptional stress response by their translocation into the nucleus and interaction with deoxyribonucleic acid. Mitochondrial-derived peptides are regulators of metabolism. This class of peptides comprises humanin, mitochondrial open reading frame of the 12S ribosomal ribonucleic acid type c (MOTS-c) and small humanin-like peptides (SHLPs). Humanin inhibits mitochondrial complex 1 activity and limits the level of oxidative stress in the cell. Data show that mitochondrial-derived peptides have a role in improving metabolic diseases, such as type 2 diabetes. Perhaps humanin can be used as a marker f…

P4550Growth differentiation factor 15 as an integrative biomarker of heart failure in patients with acute myocardial infarction

Abstract Background Growth differentiation factor 15 (GDF15), a stress-responsive cytokine member of the transforming growth factor-β family, is an emerging biomarker in cardiovascular (CV) diseases. GDF15 is weakly expressed in normal condition but increased in pathological situations such as inflammation, oxidative stress, and left ventricular remodeling. Recent data suggest GDF15 as a marker in heart failure (HF). Purpose We aimed to identify the determinants of GDF15 circulating levels in patients admitted for an acute myocardial infarction (AMI). Methods In our prospective study, all consecutive patients admitted from June 2016 to February 2018 for type 1 AMI in the Coronary Care unit …

0110 : Experimental cerebral ischemia in rats increases myocardial vulnerability to ischemia-reperfusion injury ex vivo

For years, the relationship between cardiac and neurological ischemic events has been mainly attributed to overlapping pathophysiological mechanisms and common risk factors. However, acute stroke may induce dramatic alterations of cardiovascular function. The aim of this work was to evaluate how prior cerebrovascular lesions affect myocardial function in vivo and ex vivo , as well as myocardial vulnerability to ischemic injury. Cerebral embolization was performed in adult Wistar male rats by the injection of microspheres into the left internal carotid artery. Left ventricular function, investigated in vivo using echocardiography (1 hour, 24 hours and 7 days after the embolization), was not …

Anti-Aging Effects of GDF11 on Skin

International audience; Human skin is composed of three layers: the epidermis, the dermis, and the hypodermis. The epidermis has four major cell layers made up of keratinocytes in varying stages of progressive differentiation. Skin aging is a multi-factorial process that affects every phase of its biology and function. The expression profiles of inflammation-related genes analyzed in resident immune cells demonstrated that these cells have a strong ability to regenerate adult skin stem cells and to produce endogenous substances such as growth differentiation factor 11 (GDF11). GDF11 appears to be the key to progenitor proliferation and/or differentiation. The preservation of youthful phenot…

1203Post-ischemic stroke-induced myocardial dysfunction is associated with nitro-oxidative stress and sympathetic overactivity

Association between Serum Osteoprotegerin Levels and Severity of Coronary Artery Disease in Patients with Acute Myocardial Infarction

International audience; Background. Osteoprotegerin (OPG), a glycoprotein of the tumour necrosis factor (TNF) superfamily, is one of the main biomarkers for vascular calcification. Aim. We aimed to evaluate the association between serum OPG levels and extent of coronary lesions in patients with acute myocardial infarction (MI). Methods. Consecutive patients hospitalized for an acute MI who underwent coronary angiography were included. SYNTAX score was calculated to assess the severity of coronary artery disease. The population was analysed in low (5 (3–6)), medium (11 (9–13)) and high (20 (18–23)) tertiles of SYNTAX score. Results. Among the 378 patients included, there was a gradual increa…

Dépistage séquentiel de la FA silencieuse post-AVC (Stepwise screening for silent Atrial Fibrillation After Stroke : SAFAS study)

Introduction Un tiers des AVC cryptogeniques seraient secondaires a une fibrillation atriale (FA) silencieuse non-detectee par les methodes usuelles. Trois versants seraient impliques dans le developpement d’une arythmie (le substrat atrial, le modulateur, le declencheur). Objectifs L’objectif etait d’identifier les deregulations physiopathologiques conduisant au developpement de la FA. Patients et methodes Etaient inclus les patients hospitalises pour un AVC ischemique au sein de l’USINV du CHU de Dijon, d’etiologie indeterminee a la prise en charge. Le depistage de la FA combinait de maniere sequentielle la telemetrie, le Holter ECG prolonge et le Holter sous cutane. Les donnees cliniques…

Ischemic stroke increases heart vulnerability to ischemia-reperfusion and alters myocardial cardioprotective pathways

Background and Purpose— For years, the relationship between cardiac and neurological ischemic events has been limited to overlapping pathophysiological mechanisms and common risk factors. However, acute stroke may induce dramatic changes in cardiovascular function. The aim of this study was to evaluate how prior cerebrovascular lesions affect myocardial function and signaling in vivo and ex vivo and how they influence cardiac vulnerability to ischemia-reperfusion injury. Methods— Cerebral embolization was performed in adult Wistar male rats through the injection of microspheres into the left or right internal carotid artery. Stroke lesions were evaluated by microsphere counting, tissue sta…

Brain-Heart interactions during ischemic processes: Clinical and experimental evidences

International audience

The role of osteoprotegerin in the crosstalk between vessels and bone: Its potential utility as a marker of cardiometabolic diseases

International audience; Among the numerous molecules that are being studied for their potential utility as biomarkers of cardiovascular diseases, much interest has been shown in the superfamily of tumor necrosis factor (TNF) receptors. Members of this family include osteoprotegerin (OPG) and its ligands, which are receptor activators of nuclear factor κB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). These signals may be expressed and regulated, and their functions could be involved in several physiological and pathological processes. The relationship between bone regulatory proteins and vascular biology has attracted attention, and it has been suggested that OPG may medi…

Intérêt du growth differentiation factor 15 (GDF15) comme biomarqueur pronostique après la survenue d'un Accident Vasculaire Cérébral ischémique (AVC)

Introduction Le GDF15 est un biomarqueur de mauvais pronostic dans certaines pathologies cardiovasculaires comme le syndrome coronarien aigu. Son interet dans le domaine de AVC n’a ete que peu etudie a ce jour. Objectifs Notre travail consistait a l’evaluation des taux de GDF15 chez des patients hospitalises a la phase aigue d’un AVC ischemique traites par fibrinolyse et/ou thrombectomie. L’objectif principal etait d’evaluer l’association entre les taux de GDF15 et la recuperation fonctionnelle a 3 mois. Methodes Au total, 174 patients ont ete inclus entre le 16/01 et le 30/09/2017. Le consentement etait recueilli oralement. Des prelevements biologiques ont ete realises a l’admission du pat…