Resveratrol Improves Survival, Hemodynamics and Energetics in a Rat Model of Hypertension Leading to Heart Failure

Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening −34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium–dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF

CARIOQA: Definition of a Quantum Pathfinder Mission

A strong potential gain for space applications is expected from the anticipated performances of inertial sensors based on cold atom interferometry (CAI) that measure the acceleration of freely falling independent atoms by manipulating them with laser light. In this context, CNES and its partners initiated a phase 0 study, called CARIOQA, in order to develop a Quantum Pathfinder Mission unlocking key features of atom interferometry for space and paving the way for future ambitious space missions utilizing this technology. As a cornerstone for the implementation of quantum sensors in space, the CARIOQA phase 0 aimed at defining the Quantum Pathfinder Mission's scenario and associated performance objectives. To comply with these objectives, the payload architecture has been designed to achieve long interrogation time and active rotation compensation on a BEC-based atom interferometer. A study of the satellite architecture, including all the subsystems, has been conducted. Several technical solutions for propulsion and attitude control have been investigated in order to guarantee optimal operating conditions (limitation of micro-vibrations, maximization of measurement time). A preliminary design of the satellite platform was performed.Comment: Proceedings of International Conference on Space Optics (ICSO) 2022; 3-7 October 2022; Dubrovnik; Croati

The BET bromodomain inhibitor I-BET-151 induces structural and functional alterations of the heart mitochondria in healthy male mice and rats

The bromodomain and extra-terminal domain family inhibitors (BETi) are a promising new class of anticancer agents. Since numerous anticancer drugs have been correlated to cardiomyopathy, and since BETi can affect non-cancerous tissues, we aimed to investigate in healthy animals any ultrastructural BETi-induced alterations of the heart as compared to skeletal muscle. Male Wistar rats were either treated during 3 weeks with I-BET-151 (2 or 10 mg/kg/day) (W3) or treated for 3 weeks then allowed to recover for another 3 weeks (W6) (3-weeks drug washout). Male C57Bl/6J mice were only treated during 5 days (50 mg/kg/day). We demonstrated the occurrence of ultrastructural alterations and progressive destruction of cardiomyocyte mitochondria after I-BET-151 exposure. Those mitochondrial alterations were cardiac muscle-specific, since the skeletal muscles of exposed animals were similar in ultrastructure presentation to the non-exposed animals. I-BET-151 decreased the respiration rate of heart mitochondria in a dose-dependent manner. At the higher dose, it also decreased mitochondrial mass, as evidenced by reduced right ventricular citrate synthase content. I-BET-151 reduced the right and left ventricular fractional shortening. The concomitant decrease in the velocity-time-integral in both the aorta and the pulmonary artery is also suggestive of an impaired heart function. The possible context-dependent cardiac side effects of these drugs have to be appreciated. Future studies should focus on the basic mechanisms of potential cardiovascular toxicities induced by BETi and strategies to minimize these unexpected complications

Hearts from Mice Fed a Non-Obesogenic High-Fat Diet Exhibit Changes in Their Oxidative State, Calcium and Mitochondria in Parallel with Increased Susceptibility to Reperfusion Injury

High-fat diet with obesity-associated co-morbidities triggers cardiac remodeling and renders the heart more vulnerable to ischemia/reperfusion injury. However, the effect of high-fat diet without obesity and associated co-morbidities is presently unknown.To characterize a non-obese mouse model of high-fat diet, assess the vulnerability of hearts to reperfusion injury and to investigate cardiac cellular remodeling in relation to the mechanism(s) underlying reperfusion injury.Feeding C57BL/6J male mice high-fat diet for 20 weeks did not induce obesity, diabetes, cardiac hypertrophy, cardiac dysfunction, atherosclerosis or cardiac apoptosis. However, isolated perfused hearts from mice fed high-fat diet were more vulnerable to reperfusion injury than those from mice fed normal diet. In isolated cardiomyocytes, high-fat diet was associated with higher diastolic intracellular Ca2+ concentration and greater damage to isolated cardiomyocytes following simulated ischemia/reperfusion. High-fat diet was also associated with changes in mitochondrial morphology and expression of some related proteins but not mitochondrial respiration or reactive oxygen species turnover rates. Proteomics, western blot and high-performance liquid chromatography techniques revealed that high-fat diet led to less cardiac oxidative stress, higher catalase expression and significant changes in expression of putative components of the mitochondrial permeability transition pore (mPTP). Inhibition of the mPTP conferred relatively more cardio-protection in the high-fat fed mice compared to normal diet.This study shows for the first time that high-fat diet, independent of obesity-induced co-morbidities, triggers changes in cardiac oxidative state, calcium handling and mitochondria which are likely to be responsible for increased vulnerability to cardiac insults

Gender issues in cardiovascular diseases. Focus on energy metabolism

International audienceIt is increasingly recognized that sex and gender differences (S&G) influence cardiovascular diseases (CVD), greatly impacting disease management. In terms of definition, sex refers to biological aspects, gender effects being mainly related to socio-cultural factors. Both sex and gender are interpenetrated in humans and difficult to separate. This is more clearly feasible in animal models where sex effects largely predominate. As alterations in energy metabolism are essential features of cardiovascular diseases, sexual dimorphism of energy metabolism and more specifically mitochondria occupies a place of choice. This review presents the basis of sex and gender differences in the cardiovascular pathophysiology, and how it mainly affects woman diseases, effectiveness of therapies and clinical outcome. These differences rely on complex molecular mechanisms that are still poorly understood because of the under-representation of females/women in experimental and clinical studies. Finally, the differing psychological and biological phases of woman's life are largely underestimated. This review presents an overview of the field with focus on differences in cardiac energy metabolism, which are illustrated with specific examples

Gravity Field Mapping Using Laser Coupled Quantum Accelerometers in Space

The emergence of quantum technologies, including cold atom based accelerometers, offers an opportunity to improve the performances of space geodesy missions. In this context, CNES initiated an assessment study called GRICE (GRadiom\'etrie \`a Interf\'erom\`etres quantiques Corr\'el\'es pour l'Espace) in order to evaluate the contribution of cold atom technologies to space geodesy and to the end users of geodetic data. In this paper, we present mission scenario for gravity field mapping based on a long baseline gradiometer. The mission is based on a constellation of two satellites, flying at an altitude of 373 km, each equipped with a cold atom accelerometer with a sensitivity of $6 \times 10^{-10}$~m.s$^{-2}$.$\mathrm{\tau}^{-1/2}$. A laser link measures the distance between the two satellites and couples these two instruments in order to produce a correlated differential acceleration measurement. The main parameters, determining the performances of the payload, have been investigated. We carried out a general study of satellite architecture and simulations of the mission performances in terms of restitution of the gravity field. The simulations show that this concept would give its best performance in terms of monthly gravity fields recovery under 1000~km resolution. In the resolution band between 1000 and 222~km, the improvement of the GRICE gradient approach over the traditional range-rate approach is globally in the order of 10 to 25\%

Gravity field mapping using laser-coupled quantum accelerometers in space

The emergence of quantum technologies, including cold atom based accelerometers, offers an opportunity to improve the performances of space geodesy missions. In this context, CNES initiated an assessment study called GRICE (GRadiom\'etrie \`a Interf\'erom\`etres quantiques Corr\'el\'es pour l'Espace) in order to evaluate the contribution of cold atom technologies to space geodesy and to the end users of geodetic data. In this paper, we present mission scenario for gravity field mapping based on a long baseline gradiometer. The mission is based on a constellation of two satellites, flying at an altitude of 373 km, each equipped with a cold atom accelerometer with a sensitivity of $6 \times 10^{-10}$~m.s$^{-2}$.$\mathrm{\tau}^{-1/2}$. A laser link measures the distance between the two satellites and couples these two instruments in order to produce a correlated differential acceleration measurement. The main parameters, determining the performances of the payload, have been investigated. We carried out a general study of satellite architecture and simulations of the mission performances in terms of restitution of the gravity field. The simulations show that this concept would give its best performance in terms of monthly gravity fields recovery under 1000~km resolution. In the resolution band between 1000 and 222~km, the improvement of the GRICE gradient approach over the traditional range-rate approach is globally in the order of 10 to 25\%