Gabriel Bidaux

Groupement Hospitalier Est, IHU OPERA, INSERM, University Claude Bernard Lyon 1 · Cardiology - Neurology

Significance Epidermis, the outer layer of skin, is a protective barrier and a sensing interface. Although deviation of the ambient temperature is one of the most ubiquitous stimuli affecting the skin, the influence of mild cold on epidermal homeostasis is not well understood. Using a large range of techniques, we identified a novel mild-cold senso...

The Ca2+ release in microdomains formed by intercompartmental contacts, such as mitochondria-associated endoplasmic reticulum membranes (MAMs), encodes a signal that contributes to Ca2+ homeostasis and cell fate control. However, the composition and function of MAMs remain to be fully defined. Here, we focused on the transient receptor potential va...

Gene expression orchestration is a key question in fundamental and applied research. Different models for transcription regulation were proposed, yet the dynamic regulation of RNA polymerase II (RNAP II) activity remains a matter of debate. To improve our knowledge of this topic, we investigated RNAP II motility in eukaryotic cells by combining sin...

Genetically encoded biosensors based on fluorescent proteins (FPs) are widely used to monitor dynamics and sub-cellular spatial distribution of calcium ion (Ca2+) fluxes and their role in intracellular signaling pathways. The development of different mutations in the Ca2+-sensitive elements of the cameleon probes has allowed sensitive range of Ca2+...

Despite advances in cardioprotection, new therapeutic strategies capable of preventing ischemia-reperfusion injury of patients are still needed. Here, we discover that sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase (SERCA2) phosphorylation at serine 663 is a clinical and pathophysiological event of cardiac function. Indeed, the phosphorylation leve...

Myocardial infarction (MI) is a serious cardiovascular problem that causes myocardial injury due to blood flow obstruction to a specific myocardial area. Under ischemic-reperfusion settings, a burst of reactive oxygen species is generated, leading to redox imbalance that could be attributed to several molecules, including myoglobin. Myoglobin is dy...

Objective: The ProCCard study tested whether combining several cardioprotective interventions would reduce the myocardial and other biological and clinical damage in patients undergoing cardiac surgery. Design: Prospective, randomized, controlled trial. Setting: Multicenter tertiary care hospitals. Participants: 210 patients scheduled to und...

Rationale: Mitochondria are key organelles involved in cell survival and death during the acute phenomena of myocardial ischemia-reperfusion (i.e., myocardial infarction). To investigate the functions of isolated mitochondria such as calcium retention capacity, oxidative phosphorylation, and reactive oxygen species (ROS) production, already establ...

Gene expression orchestration is a key question in fundamental and applied research. Different models for transcription regulation were proposed, yet the dynamic regulation of RNA polymerase II (RNAP II) activity remains a matter of debate. To improve our knowledge of this topic, we investigated RNAP II motility in eukaryotic cells by combining Sin...

Genetically encoded biosensors based on fluorescent proteins (FPs) are widely used to monitor dynamics and sub-cellular spatial distribution of calcium ion (Ca2+) fluxes and their role in intracellular signaling pathways. The development of different mutations in the Ca2+-sensitive elements of the cameleon probes has allowed sensitive range of Ca2+...

Introduction: Hepatocyte Growth Factor (HGF) is a cytokine promoting cell survival via its receptor c-met. Heparin injection is known to induce a massive release of native HGF in blood. Heparin is used at the acute phase of myocardial infarction (MI). However, HGF release at the acute phase of MI and its potential cardioprotective effect is unknown...

Introduction: Despite advances in cardioprotection, new therapeutic strategies capable of preventing acute myocardial ischemia-reperfusion injury and reducing secondary event of patients are still needed. Hypothesis: We hypothesized that limitation of SERCA2 phosphorylation on a serine/threonine residue at reperfusion could provide protection again...

Introduction: CCL5 or RANTES is a chemokine that mediates chemotaxis and activation of T cells, monocytes, granulocytes, mast cells and dendritic cells. It is involved in the pathogenesis of several diseases including atherosclerosis but little is known about its role at the acute phase of myocardial infarction (MI). Hypothesis: We questioned wheth...

Heart transplantation is facing a shortage of grafts. Donation after Circulatory Death (DCD) would constitute a new potential of available organs. In the present work, we aimed to evaluate whether Postconditioning (ischemic or with ciclosporin-A (CsA)) could reduce ischemia-reperfusion injury in a cardiac arrest model when applied at the start of r...

Introduction L’arrêt cardiaque (AC) récupéré provoque une ischémie-reperfusion rénale (IRR), qui peut conduire à l’insuffisance rénale aiguë (IRA). Nous avons étudié l’intérêt de eCIRP (extracellular Cold-Inducible RNA-binding Protein) plasmatique comme potentiel biomarqueur prédictif d’IRA après IRR. Description L’intérêt de eCIRP était évalué da...

Objectives To assess the relationship between blood biomarkers of inflammation and lesion growth within the penumbra in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). Methods HIBISCUS-STROKE cohort enrolled patients admitted in the Lyon Stroke Center for an anterior circulation AIS treated with MT following MRI. Le...

Renal ischemia-reperfusion (IR) injury can lead to acute kidney injury, increasing the risk of developing chronic kidney disease. We hypothesized that mild therapeutic hypothermia (mTH), 34 °C, applied during ischemia could protect the function and structure of kidneys against IR injuries in mice. In vivo bilateral renal IR led to an increase in pl...

The orchestration of gene expression is a key question in both fundamental and applied research. Different models for transcription regulation were proposed, yet the dynamic regulation of RNA polymerase II (RNAP II) activity remains a matter of debate. To improve our knowledge of this topic, we investigated RNAP II motility in eukaryotic cells by c...

Uncertainty exists regarding whether cyclophilin D (CypD), a mitochondrial matrix protein that plays a key role in ischemia-reperfusion injury, can be a pharmacological target for improving outcomes after cardiac arrest (CA), especially when therapeutic hypothermia is used. Using CypD knockout mice (CypD-/-), we investigated the effects of loss of...

Introduction The protection against reperfusion injury conferred by ischemic post-conditioning (IPoC) has been reported to rely on several signalization pathways like RISK and SAFE. However, their respective roles and the downstream-mechanisms involved are not fully understood S727 STAT3 has been proposed to be required for STAT3 translocation to m...

Introduction Ischemic heart disease is one of the leading cause of death and disability worldwide. Calcium handling in the post-ischemic myocardium is a prime target to treat patients with acute myocardial infarction. Although SERCA2 is a promising target for the treatment of Ca2+ dyshomeostasis and contractile dysfunction following ischemia-reperf...

Introduction Myocardial infarction (MI) is a major threat worldwide and despite progress in clinical care, its morbi-mortality is still high. In the last decades, therapeutic strategies attempted to preserve cardiomyocytes from death, but clinical trials failed to translate them to the clinic. MI is associated with a strong inflammatory reaction an...

Introduction Ischemia-reperfusion (IR) leads to systemic inflammation. Mild therapeutic hypothermia (mTH) has been suggested to bring protection against IR lesions. However, mTH remains limited to intensive care units (ICU) after resuscitated cardiac arrest (rCA) and is not currently used in nephrology. Extracellular cold-inducible RNA-binding prot...

Introduction Heart failure with preserved ejection fraction (HFpEF) has nowadays become a major public health issue worldwide. HFpEF is usually associated with metabolic syndrome (MS) such as type II diabetes. A growing attention has been shed on Δ9-desaturase (SCD1), the bottleneck enzyme in the mono-desaturation of fatty acids. Indeed, SCD1 contr...

Background Aging is associated with a chronic low-grade inflammatory state. This condition may affect the acute inflammatory response involved in ST-segment–elevation myocardial infarction (STEMI) or acute ischemic stroke (AIS). We sought to compare the profile of a set of circulating inflammatory markers between young and older patients admitted f...

Hypothermia provides an effective neuro and cardio-protection in clinical settings implying ischemia/reperfusion injury (I/R). At the onset of reperfusion, succinate-induced reactive oxygen species (ROS) production, impaired oxidative phosphorylation (OXPHOS), and decreased Ca2+ retention capacity (CRC) concur to mitochondrial damages. We explored...

Background: As inflammation following ST-segment elevation myocardial infarction (STEMI) is both beneficial and deleterious, there is a need to find new biomarkers of STEMI severity. Objective: We hypothesized that the circulating concentration of the soluble tumor necrosis factor α receptors 1 and 2 (sTNFR1 and sTNFR2) might predict clinical outco...

Introduction L’ischémie-reperfusion rénale crée des lésions vasculaires aiguës, qui peuvent se chroniciser. Notre but était de montrer que l’échographie rénale de contraste permet d’évaluer les anomalies de perfusion rénale après ischémie-reperfusion. Description Une ischémie rénale unilatérale de 15 minutes par clampage du pédicule vasculaire rén...

Introduction L’ischémie-reperfusion rénale est à l’origine d’une inflammation rénale et systémique. Il est suggéré un effet protecteur de l’hypothermie modérée. Nous avons dosé extracellular Cold-Inducible RNA-binding Protein (eCIRP) plasmatique, une cytokine pro-inflammatoire, après une ischémie rénale avec ou sans hypothermie. Description Une is...

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Background Inflammation is a key factor of myocardial damage in reperfused ST-segment–elevation myocardial infarction. We hypothesized that colchicine, a potent anti-inflammatory agent, may reduce infarct size (IS) and left ventricular (LV) remodeling at the acute phase of ST-segment–elevation myocardial infarction. Methods In this double-blind mu...

Objectives: To determine whether continuous IV infusion of molar sodium lactate would limit cardiac arrest-induced neurologic injury and cardiovascular failure. Design: Randomized blinded study (animal model). Setting: University animal research facility. Subjects: Twenty-four adult male "New Zealand White" rabbits. Interventions: Anesthet...

Background and Aims Renal ischemia-reperfusion can lead to acute kidney injury (AKI), increasing the risk of developing chronic kidney disease (CKD) through inflammation and vascular lesions. Serum urea or creatinine level routinely used as diagnostic indices of renal function are always delayed from the onset of the disease. Therefore, we currentl...

Introduction Leptin, an adipocyte derived hormone, plays a central role in food intake regulation but also in inflammation regulation. Leptin level is increased after myocardial infarction but its relationship with clinical prognosis is unknown. Objective The study objective was to evaluate, in a cohort of patients admitted for ST elevation myocar...

Background: Soluble vascular cell adhesion molecule-1 (sVCAM-1) is a biomarker of endothelial activation and inflammation. There is still controversy as to whether it can predict clinical outcome after ST-elevation myocardial infarction (STEMI). Our aim was to assess the sVCAM-1 kinetics and to evaluate its prognostic predictive value. Method: W...

Following a prolonged exposure to hypoxia–reoxygenation, a partial disruption of the ER-mitochondria tethering by mitofusin 2 (MFN2) knock-down decreases the Ca2+ transfer between the two organelles, limits mitochondrial Ca2+ overload and prevents the Ca2+-dependent opening of the mitochondrial permeability transition pore, i.e., limits cardiomyocy...

Mitochondria are important cell-death checkpoints and mitochondrial Ca²⁺ overload is considered as a potent apoptotic intrinsic pathway inducer. Here, we report that this Ca²⁺ apoptosis link is largely ineffective in inducing cell-death just by itself and required a concomitant inhibition of autophagy to counteract its pro-survival action. In such...

During myocardial infarction, dysregulation of Ca2+ homeostasis between the reticulum, mitochondria, and cytosol occurs in cardiomyocytes and leads to cell death. Ca2+ leak channels are thought to be key regulators of the reticular Ca2+ homeostasis and cell survival. The present study aimed to determine whether a particular reticular Ca2+ leak chan...

Control of cell death/survival balance is an important feature to maintain tissue homeostasis. Dependence receptors are able to induce either survival or cell death in presence or absence of their ligand, respectively. However, their precise mechanism of action and their physiological importance are still elusive for most of them including the MET...

Background Ischemic heart diseases are a major cause of death worldwide. Different animal models, including cardiac surgery, have been developed over time. Unfortunately, the surgery models have been reported to trigger an important inflammatory response that might be an effect modifier, where involved molecular processes have not been fully elucid...

Signal transducer and activator of transcription 3 (STAT3) is a signaling molecule and transcription factor that plays important protective roles in the heart. The protection mediated by STAT3 is attributed to its genomic actions as a transcription factor and other non-genomic roles targeting mitochondrial function and autophagy. As a transcription...

How nuclear proteins diffuse and find their targets remains a key question in the transcription field. Dynamic proteins in the nucleus are classically subdiffusive and undergo anomalous diffusion, yet the underlying physical mechanisms are still debated. In this study, we explore the contribution of interactions to the generation of anomalous diffu...

Calcium (Ca2+) homeostasis is essential for cell survival and is precisely controlled by several cellular actors such as the sarco/endoplasmic reticulum and mitochondria. Upon stress induction, Ca2+ released from sarco/endoplasmic reticulum stores and from extracellular Ca2+ pools accumulates in the cytosol and in the mitochondria. This induces Ca2...

Introduction Myocardial infarction is an irreversible death of cardiac cells in response to prolonged ischemia and ischemia-reperfusion injury. Experimental designs and analytical pipelines used in time-series ischemia-reperfusion (IR) transcriptomic studies represent major challenges in the understanding of progression of such multifactorial disea...

Introduction STAT3 exerts Cardioprotective roles against the ischemia/reperfusion injury (IRI) and during ischemic post-conditioning (IPoC). In cell line models, STAT3 can be phosphorylated on its tyrosine705 and serine727 residues. The involvement of STAT3 in IPoC, its interlink with MAPKS and the specific roles of its Y705 and S727 residues in mo...

Genes showing versatile functions or subjected to fast expansion and contraction during the adaptation of species to specific ecological conditions, like sensory receptors for odors, pheromones and tastes, are characterized by a great plasticity through evolution. One of the most fascinating sensory receptors in the family of TRP channels, the cold...

The signal transducer and activator of transcription 3, STAT3, transfers cellular signals from the plasma membrane to the nucleus, acting as a signaling molecule and a transcription factor. Reports proposed an additional non-canonical role of STAT3 that could regulate the activity of complexes I and II of the electron transport chain and the openin...

Introduction STAT3 is required for the cardioprotective effect of ischemic post-conditioning (IPoC). The mechanisms involved in its effects are poorly understood and are most often evaluated in cell lines not cardiomyocytes. In addition, few studies have reported a cross-analysis of the STAT3 pathway and other signaling pathways activated by IPoC....

Introduction Myocardial infarction (MI) is a leading cause of death worldwide. Although some targets associated with MI are extensively studied, their dynamic characteristics of gene expressions during the disease progression haven’t been fully elucidated yet. Objectives In this study, we aim to measure the dynamic regulation of gene expression du...

In order to further understand genetic expression in eukaryotic cells, we combine several molecular dynamics analysis technics in one microscopy module. This module can perform confocal (CLSM), wide field (TIRFM/HiLo) and light-sheet illuminations.

Photodynamic therapy (PDT) has developed into a new clinical and non-invasive treatment for cancer over the past 30 years. By the combination of three non toxic partners i.e. a photosensitizer (PS), molecular oxygen (O2) and light, cytotoxic reactive oxygen species (ROS) are locally produced leading to irreversible vascular and cellular damages. In...

Most cell physiology events are dictated by the integration of perceived signals and the elaboration by cells of adapted answers via the execution of proper transcriptional programs. In order to ensure an optimal control of these answers, many regulation mechanisms have been selected throughout the evolution, thus allowing to fine-tune transcript e...

Introduction STAT3 exerts Cardioprotective roles against the ischemia/reperfusion injury (IRI) and during ischemic postconditioning (IPoC). An additional mitochondrial protective role has evolved. In cell line models, STAT3 can be phosphorylated on its tyrosine705 and serine727 residues. The involvement of STAT3 in IPoC, its mitochondrial localizat...

Introduction Myocardial infarction leads to ischemia reperfusion (I/R) injury. The quantification of tissue injury is essential in translational research. Although MRI or X-ray scanner can estimate injured area in live animals, their cost and their limited accessibility often restrict their use. Actually, the commonly used method is the TTC blue te...

Introduction Myocardial infarction (MI) is a leading cause of death worldwide. Although some targets associated with MI have been extensively studied, their dynamic characteristics in gene expressions during the disease progression haven’t been fully elucidated to date. Objectives In this study, we aim to measure the dynamic regulation of gene exp...