Low Density Lipoprotein Cholesterol Decreases the Expression of Adenosine A2A Receptor and Lipid Rafts-Protein Flotillin-1: Insights on Cardiovascular Risk of Hypercholesterolemia

International audienceHigh blood levels of low-density lipoprotein (LDL)-cholesterol (LDL-C) are associated with atherosclerosis, mainly by promoting foam cell accumulation in vessels. As cholesterol is an essential component of cell plasma membranes and a regulator of several signaling pathways, LDL-C excess may have wider cardiovascular toxicity. We examined, in untreated hypercholesterolemia (HC) patients, selected regardless of the cause of LDL-C accumulation, and in healthy participants (HP), the expression of the adenosine A2A receptor (A2AR), an anti-inflammatory and vasodilatory protein with cholesterol-dependent modulation, and Flotillin-1, protein marker of cholesterol-enriched plasma membrane domains. Blood cardiovascular risk and inflammatory biomarkers were measured. A2AR and Flotillin-1 expression in peripheral blood mononuclear cells (PBMC) was lower in patients compared to HP and negatively correlated to LDL-C blood levels. No other differences were observed between the two groups apart from transferrin and ferritin concentrations. A2AR and Flotillin-1 proteins levels were positively correlated in the whole study population. Incubation of HP PBMCs with LDL-C caused a similar reduction in A2AR and Flotillin-1 expression. We suggest that LDL-C affects A2AR expression by impacting cholesterol-enriched membrane microdomains. Our results provide new insights into the molecular mechanisms underlying cholesterol toxicity, and may have important clinical implication for assessment and treatment of cardiovascular risk in HC

Correlation between low adenosine A2A receptor expression and hypercholesterolemia: A new component of the cardiovascular risk?

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A2 Adenosine Receptor Subtypes Overproduction in Atria of Perioperative Atrial Fibrillation Patients Undergoing Cardiac Surgery: A Pilot Study

International audienceObjective: Although atrial fibrillation is a common cardiac arrhythmia in humans, the mechanism that leads to the onset of this condition is poorly elucidated. Adenosine is suspected to be implicated in the trigger of atrial fibrillation (AF) through the activation of its membrane receptors, mainly adenosine receptor (AR) subtypes A 1 R and A 2 R. In this study, we compared blood adenosine concentration (BAC), and A 1 R, A 2A R, and A 2B R production in right (RA) and left atrium (LA), and on peripheral blood mononuclear cells (PBMCs) in patients with underlying structural heart disease undergoing cardiac surgery with or without peri-operative AF (PeOpAF). Methods: The study group consisted of 39 patients (30 men and 9 women, mean age, range 65 [40–82] years) undergoing cardiac surgery and 20 healthy patients (8 women and 12 men; mean age, range 60 [39–72] years) as controls were included. Among patients, 15 exhibited PeOpAF. Results: Blood adenosine concentration was higher in patients with PeOpAF than others. A 2A R and A 2B R production was higher in PBMCs of patients compared with controls and was higher in PeOpAF patients than other patients. In LA and RA, the production of A 2A R and A 2B R was higher in patients with PeOpAF than in other patients. Both A 2A R and A 2B R production were higher in LA vs. RA. A 1 R production was unchanged in all situations. Finally, we observed a correlation between A 1 R, A 2A R, and A 2B R production evaluated on PBMCs and those evaluated in LA and RA. Conclusions: Perioperative AF was associated with high BAC and high A 2A R and A 2B R expression, especially in the LA, after cardiac surgery in patients with underlying structural heart disease. Whether these increases the favor in triggering the AF in this patient population needs further investigation

BRACAVENIR: an observational study of expectations and coping in young women with high hereditary risk of breast and ovarian cancer

Abstract Background In families with high risk of hereditary breast/ovarian cancer (HBOC), women before age 30 do not yet undergo clinical screening, but they are exposed to contradictory information from diverse sources. They may be presented with surgical prevention options at a key moment of their identity construction, the start of a marital relationship and/or at the onset of procreation projects. We tested an original psychoeducational intervention to help these women better cope with these difficult issues. Methods Seven young female counselees (26.4 ± 2.9 years [23–30]) from the Oncogenetics Department at Jean Perrin Comprehensive Cancer Center were enrolled. A weekend group workshop composed of short conferences, group sharing and role playing activities was supervised by a psychotherapist. A longitudinal analysis of questionnaires over one year of follow-up was performed. The Herth Hope Inventory was evaluated, as well as self-esteem, anxiety, perceived control, coping, and quality of life. Participants’ comments were collected by a genetic counselor throughout the workshop. Results All participants were BRCA mutation carriers and six had lived with a close relative affected by breast/ovarian cancer. Hope, self-esteem and quality of life increased during the year after the workshop (p = 0.0003). Coping by focus on the problem increased in the first 6 months (p = 0.011) and returned to baseline values at one year, while coping by focus on emotions decreased steadily (p = 0.021). Debriefing from the workshop highlighted the new medical opportunities proposed and the challenges these young women face, such as whether to have prophylactic surgery, and if so before or after having children, and how surgery might affect their relationship with their partner. Conclusion A tailored two-day psychoeducational workshop may be sufficient to improve the way young women with BRCA mutations deal with the implications of HBOC risk. Trial registration BRACAVENIR was registered in ClinicalTrials.gov with no NCT02705924

Stimulated thyroglobulin and Thyroglobulin Reduction Index Predict Excellent Response in Differentiated Thyroid Cancers

International audienceDespite its good prognosis, differentiated thyroid cancer (DTC) is characterized by a high risk of disease persistence and/or recurrence. Estimation of long-term remission (excellent response) thanks to specific parameters could help to personalize the schedule of active surveillance

Lavoisier manuscript collection.

The Lavoisier manuscript collection (1766-1834) contains materials by, to or about Antoine Laurent Lavoisier and his wife, Marie-Anne-Pierrette Lavoisier, including material on their scientific work, correspondence, manuscripts, certificates, deeds, contracts, plates for publications, maps and drawings, memorabilia and artifacts. Letters include correspondence with the Académie des Sciences, Jean Sylvain Bailly, François Baudon, Anne-Margueritte-Charlotte Baudon, Antoine Baumé, Claude-Louis Berthollet, Jean-Antoine-Claude Chaptal, Joseph Black, Henri Louis Duhamel du Monceau, Auguste Denis Fougeroux de Bondaroy, Antoine-François de Fourcroy, Benjamin Franklin (photocopy of one letter), Jean-Antoine Lavoisier, Joseph Louis Lagrange, Marie-Anne-Pierrette Lavoisier, Gaspard Monge, Jacques Paulze, and the Régie des Poudres et Salpêtres. Other documents relate to Benoist LaForte, the Ferme Générale, the Académie des Sciences, Mathurin-Jacques Brisson, Joseph Priestley, the Régie des Poudres et Salpêtres, and other aspects of Lavoisier's life and work and those of his associates.Antoine Laurent Lavoisie (born 1743) and his wife, Marie-Anne-Pierrette Lavoisier (born 1758) were both French chemists. The Lavoisier manuscript collection (1766-1834) contains materials by, to or about Antoine and Marie, including material on their scientific work, correspondence, manuscripts, certificates, deeds, contracts, plates for publications, maps and drawings, memorabilia and artifacts.Physical Description note: Manuscripts, drawings, prints, artifacts.The Lavoisier manuscript collection (1766-1834) contains materials by, to or about Antoine Laurent Lavoisier and his wife, Marie-Anne-Pierrette Lavoisier, including material on their scientific work, correspondence, manuscripts, certificates, deeds, contracts, plates for publications, maps and drawings, memorabilia and artifacts. Letters include correspondence with the Académie des Sciences, Jean Sylvain Bailly, François Baudon, Anne-Margueritte-Charlotte Baudon, Antoine Baumé, Claude-Louis Berthollet, Jean-Antoine-Claude Chaptal, Joseph Black, Henri Louis Duhamel du Monceau, Auguste Denis Fougeroux de Bondaroy, Antoine-François de Fourcroy, Benjamin Franklin (photocopy of one letter), Jean-Antoine Lavoisier, Joseph Louis Lagrange, Marie-Anne-Pierrette Lavoisier, Gaspard Monge, Jacques Paulze, and the Régie des Poudres et Salpêtres. Other documents relate to Benoist LaForte, the Ferme Générale, the Académie des Sciences, Mathurin-Jacques Brisson, Joseph Priestley, the Régie des Poudres et Salpêtres, and other aspects of Lavoisier's life and work and those of his associates.Antoine Laurent Lavoisie (born 1743) and his wife, Marie-Anne-Pierrette Lavoisier (born 1758) were both French chemists. The Lavoisier manuscript collection (1766-1834) contains materials by, to or about Antoine and Marie, including material on their scientific work, correspondence, manuscripts, certificates, deeds, contracts, plates for publications, maps and drawings, memorabilia and artifacts.Lavoisier Manuscripts and Graphics Collection, #4712. Division of Rare and Manuscript Collections, Cornell University Library.Mode of access: Internet.After Antoine Laurent Lavoisier's death, his properties were consficated by the State. In 1795, after a campaign, Marie-Anne Lavoisier obtained the restoration of her property. In the same time, she published an edition of Lavoisier's works. In 1805, she married an American scientist, Benjamin Thomson, who had become Count Rumford in 1791.In 1789, Lavoisier failed to be elected at the Estates General, and steered clear of political affairs. He resigned from his office at the Ferme Générale shortly before its abolition in 1791, but was considered as an consultant in financial affairs and became the director of the Discount Bank, and a commissioner of the Public Treasury, and expressed many ideas about the reforms of French public finance and taxation. At the same time, he took part to the major reform of the unification of the weights and measures system. But, as a former Fermier Général and like his peers, among them his father-in-law, Jacques Paulze, he was arrested in 1794. They were accused of exactions and embezzlement and transferred to the Conciergerie. On the 19 floréal an II (May 8, 1794), they were all sentenced to death and executed.Simultaneously, from 1772, Lavoisier studied pneumatic chemistry, the chemistry of gases, borrowing experimental facts from English scientists, like Priestley. In 1773, he published the Opuscules physiques et chimiques , where he considered atmospheric air as a mixture, that established his reputation as a chemist. In the 1770's, he discovered that the components of air were mainly oxygen and nitrogen, and defined combustion and calcination as chemical reactions. Then, with Guyton de Morveau, Berthollet and Fourcroy he elaborated a new method of chemical nomenclature, giving chemistry a clear language, published in 1787 under the title of Méthode de nomenclature chimique . At least, in 1789, his Traité élémentaire de chimie explained the essential points of the new chemistry, like the composition of air and water and the law of the conservation of matter in chemical reactions, and depicted the experimental methods of a real scientific approach. The thirteen plates illustrating the work had been engraved by Marie-Anne LavoisierIn 1768, he was admitted to the Académie des Sciences, where he presented his research on the chemical analysis of water. The same year, he entered the Ferme Générale, a private company in charge of collecting indirect taxes for the king. Lavoisier became first an inspector of one of the Ferme Générale commissions, the Tobacco commission, where his supervisor was Jacques Paulze. On December 16, 1771, Lavoisier married his thirteen-year-old daughter, Marie-Anne-Pierrette Paulze, who was also the grandniece of the powerful Abbé Terray, the Controller General of Finance. In 1775, Lavoisier entered the Régie des Poudres et Salpêtres, a private company responsible for the production, control and refining of saltpeter and the manufacture of gunpowder in France. As a Fermier Général and a member of the Régie des Poudres et Salpêtres, Lavoisier became interested in economic theories, physiocratic ideas, agronomy, and public finance.Antoine Laurent Lavoisier was born in Paris in 1743. He was the son of Jean Antoine Lavoisier, a lawyer, and Émilie Punctis, who belonged to a wealthy Parisian family, and died when he was two. Then he attended the Collège Mazarin where he studied classics and mathematics. In 1763, he passed the Bachelor of Law degree. At this time he got interested in mineralogy and chemistry and attended Rouelle's classes. In 1766-1767, he went on some field trips with Jean Etienne Guettard, to study the stratigraphy of soils and make an inventory of the mineralogical resources of France.The bulk of the collection came down through the Chazelles family and was subsequently acquired by Lavoisier bibliographer Denis Duveen. Duveen sold the collection after finishing the bibliography. The Cornell Library purchased the collection from dealer H.P. Kraus in 1963. Additional material was collected by Pierre Dejours, and subsequently the Library purchased the Dejours material from Librairie Hatchuel in 2006