A5075346652- Estrogen and related hormone effects
- Nitric Oxide and Endothelin Effects
- Hormonal Regulation and Hypertension
- Angiogenesis and VEGF in Cancer
- Menopause: Health Impacts and Treatments
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Eicosanoids and Hypertension Pharmacology
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Adenosine and Purinergic Signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nuclear Receptors and Signaling
- Atherosclerosis and Cardiovascular Diseases
- Immune cells in cancer
- Apelin-related biomedical research
- Cardiac Ischemia and Reperfusion
- Renin-Angiotensin System Studies
- Ion channel regulation and function
- Complement system in diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- MicroRNA in disease regulation
- Receptor Mechanisms and Signaling
- Liver Disease and Transplantation
- Blood Coagulation and Thrombosis Mechanisms
- Inflammatory mediators and NSAID effects
Inserm
2014-2023
Centre National de la Recherche Scientifique
2015-2023
Université d'Angers
2015-2023
Université de Strasbourg
2022-2023
Laboratoire de Chémo-biologie synthétique et thérapeutique
2023
Mitochondrial and Cardiovascular Physiopathology
2021
Université de Rouen Normandie
2003-2021
Normandie Université
2018-2021
Biomatériaux et Bioingénierie
2021
École Polytechnique Fédérale de Lausanne
2017
Highlights•Design of a novel high-throughput assay for cellular mechanosensation•An RNAi screen identifies GPR68 as mechanosensor•GPR68 is necessary and sufficient responses to fluid shear stress•GPR68 required flow-induced dilation remodeling in miceSummaryMechanotransduction plays crucial role vascular biology. One example this the local regulation resistance via flow-mediated (FMD). Impairment process hallmark endothelial dysfunction precursor wide array diseases, such hypertension...
Toll-like receptors (TLR) 2 are expressed in cardiac and inflammatory cells, regulate leukocyte function. Because adhesion is a critical event endothelial injury induced by ischemia/reperfusion (I/R), we assessed whether TLR2 were involved I/R-induced coronary injury.Ischemia-reperfusion markedly decreased NO-mediated relaxations to acetylcholine ex vivo. In contrast, deficient mice, I/R paradoxically improved the responses acetylcholine. To precise cellular compartment expressing which...
Microparticles (MPs) are small fragments generated from the plasma membrane after cell stimulation.Among candidate proteins harbored by MPs, we recently showed that sonic hedgehog (Shh) is present in MPs activated/apoptotic human T lymphocytes [Martı ´nez et al., Blood (2006) vol.108, 3012-3020].We show here Shh carried induces nitric oxide (NO) release endothelial cells, triggers changes expression and phosphorylation of enzymes related to NO pathway, decreases production reactive oxygen...
Cytochrome-derived epoxyeicosatrienoic acids may be important endothelium-derived hyperpolarizing factors, opening calcium-activated potassium channels, but their involvement in the regulation of arterial stiffness during changes blood flow humans is unknown. In healthy volunteers, we measured pressure, radial artery diameter, wall thickness, and (NIUS02) hand skin heating presence saline or inhibitors NO synthase (N(G)-monomethyl-L-arginine), channels (tetraethylammonium), cytochrome...
Rationale: Cerebrovascular function is critical for brain health, and endogenous vascular protective pathways may provide therapeutic targets neurological disorders. S1P (Sphingosine 1-phosphate) signaling coordinates functions in other organs, 1 (S1P receptor-1) modulators including fingolimod show promise the treatment of ischemic hemorrhagic stroke. However, also lymphocyte trafficking, lymphocytes are currently viewed as principal target modulation Objective: To address roles mechanisms...
Inhibition of aldosterone synthase, the key enzyme in formation, could be an alternative strategy for mineralocorticoid-receptor antagonists congestive heart failure (CHF), but its effect CHF is unknown.We compared, rats with CHF, effects a 7 day and 12 week treatment synthase inhibitor FAD286 (4 mg kg(-1) day(-1)) those induced by spironolactone (80 day(-1)). FAD286/spironolactone increased cardiac output without modifying arterial pressure. Long-term reduced left ventricular (LV)...
Mineralocorticoid receptor (MR) antagonists slow down the progression of heart failure after myocardial infarction (MI), but cell-specific role MR in these benefits is unclear. In this study, expressed vascular smooth muscle cells (VSMCs) was investigated. Two months coronary artery ligation causing MI, mice with VSMC-specific deletion (MI-MR(SMKO)) and treated antagonist finerenone (MI-fine) had improved left ventricular compliance elastance when compared infarcted control (MI-CTL), as well...
Background Although estrogen receptor α ( ER α) acts primarily as a transcription factor, it can also elicit membrane‐initiated steroid signaling. Pharmacological tools and transgenic mouse models previously highlighted the key role of signaling in 2 actions estrogens endothelium: increase NO production acceleration reendothelialization. Methods Results Using mice with mutated at cysteine 451 (ERaC451A), recognized palmitoylation site required for plasma membrane location, disruption nuclear...
Cardiomyocyte-specific overexpression of aldosterone synthase in male (MAS) mice induces a nitric oxide-independent coronary dysfunction. Because calcium-activated potassium (BKCa) channels are essential for vascular smooth muscle cell (VSMC) relaxation, we hypothesized that alters their expression and/or function VSMCs.Left artery segments were isolated from MAS or wild-type and mounted wire myograph. Responses to acetylcholine assessed (in the presence oxide inhibitor) without with...
To assess the coronary endothelial protective effects of 17β-estradiol (E2) and role estrogen receptor (ER) α in ischemia/reperfusion (I/R).E2 exerts cardiac I/R. However, implication vivo endothelium cellular targets anti-ischemic E2 are unknown. Mice were subjected to I/R (30 minutes I 1 hour R) vivo, after which acetylcholine-induced relaxation isolated segments was assessed ex vivo. induced a dysfunction untreated ovariectomized mice that prevented by long-term treatment with wild-type,...
Although 17beta-estradiol (E2) is protective in experimental models of myocardial and brain ischemia, its effect on skin ischemia remains unknown. Here, we assessed the E2 a mouse model mimicking surgery flaps. Whereas necrosis appeared half portion flap within 1 week after ovariectomized mice, it was reduced up to 10-fold when mice were pretreated with E2, at least 3 days before surgery. The beneficial be attributable an increase survival, revealed by measuring viability ex vivo explants...
The deleterious effects of aldosterone excess demonstrated in cardiovascular diseases might be linked part to coronary vascular dysfunction. However, whether such dysfunction is a cause or consequence the changes occurring cardiomyocytes unclear. Moreover, possible link between mineralocorticoid receptor (MR)-mediated on cardiomyocyte and arteries unknown. Thus we used mouse model with conditional, cardiomyocyte-specific overexpression human MR (hMR) observed endothelial function isolated...
Preconditioning with brief periods of ischemia-reperfusion (I/R) induces a delayed protection coronary endothelial cells against reperfusion injury. We assessed the possible role nitric oxide (NO) produced during prolonged I/R as mediator this protection. Anesthetized rats were subjected to 20-min cardiac ischemia/60-min reperfusion, 24 h after sham surgery or preconditioning (1 × 2-min ischemia/5-min and 2 5-min reperfusion). The nonselective NO synthase (NOS) inhibitor l-NAME, selective...
Objective: ERα (estrogen receptor alpha) exerts nuclear genomic actions and also rapid membrane-initiated steroid signaling. The mutation of the cysteine 451 into alanine in vivo has recently revealed key role this palmitoylation site on some vasculoprotective 17β-estradiol (E2) fertility. Here, we studied arginine 260 which been described to be involved its E2-induced signaling with PI-3K (phosphoinositide 3-kinase) as well G protein cultured cell lines. Approach Results: We generated a...
Myogenic vasoconstriction is an autoregulatory function of small arteries. Recently, G-protein-coupled receptors have been involved in myogenic vasoconstriction, but the downstream signalling mechanisms and in-vivo-function this autoregulation are poorly understood. Here, we show that arteries from mice with smooth muscle-specific loss G 12 /G 13 or Rho guanine nucleotide exchange factor ARHGEF12 lost vasoconstriction. This defect was accompanied by RhoA activation, while vessels showed...
Background The cardiovascular protective effects of estrogens in premenopausal women depend mainly on estrogen receptor α (ERα). ERα activates nuclear gene transcription regulation and membrane-initiated signaling. latter plays a key role estrogen-dependent activation endothelial NO synthase. goal the present work was to determine respective roles 2 activities function cardiac kidney damage young old female mice with hypertension, which is major risk factor postmenopausal women. Methods...
Estrogen receptor alpha (ERα) activation by estrogens prevents atheroma through its nuclear action, whereas plasma membrane-located ERα accelerates endothelial healing. The genetic deficiency of was associated with a reduction in flow-mediated dilation (FMD) one man. Here, we evaluated ex vivo the role on FMD resistance arteries. FMD, but not agonist (acetylcholine, insulin)-mediated dilation, reduced male and female mice lacking ( Esr1 -/- mice) compared to wild-type dependent presence...
Bioinspired adhesives have been increasingly developed, especially towards a biomedical application. Therefore, in this study, dopamine (DA) was oxidized into polydopamine (PDA) gelatin mixture via titration with NaIO4 as strong oxidant to easily obtain an adhesive antioxidant and self-healing PDA–gelatin hydrogel. Rheology experiments show stiffness the order of kPa thermal resistance above 50 °C, much gel–sol transition temperature pristine gelatin. After heating at 55 gel is self-healing....
Abstract A premature atherosclerosis has been presumed in patients with antiphospholipid syndrome. The potential role of antibodies the development atheroma is rather controversial. In this study, we tested hypothesis that could induce via vascular functional changes. CD1 mice received one single injection monoclonal derived from male (BXSB × NZW) F1 a lupus-like disease associated an syndrome and coronary artery disease. One week later, first-order mesenteric arteries (diameter 220–260 μm)...
Objective: Hemorrhagic shock followed by resuscitation (HS/R) promotes organ injury priming cells of the innate immune system for inflammatory response. Toll-like receptors (TLRs) play an important role in signal transduction shock/resuscitation conditions. Because proinflammatory mediators are a critical event mesenteric endothelial induced HS/R, we assessed TLR4 or TLR2 this setting. Design: Laboratory investigation. Setting: Research laboratory at Rouen University Medical School....