Search

Inflammatory responses in small vessels play an important role in the development of cardiovascular diseases, including hypertension, stroke, and small vessel disease. This involves various complex molecular processes including oxidative stress, inflammasome activation, immune-mediated responses, and protein misfolding, which together contribute to microvascular damage. In addition, epigenetic factors, including DNA methylation, histone modifications, and microRNAs influence vascular inflammation and injury. These phenomena may be acquired during the aging process or due to environmental factors. Activation of proinflammatory signaling pathways and molecular events induce low-grade and chronic inflammation with consequent cardiovascular damage. Identifying mechanism-specific targets might provide opportunities in the development of novel therapeutic approaches. Monoclonal antibodies targeting inflammatory cytokines and epigenetic drugs, show promise in reducing microvascular inflammation and associated cardiovascular diseases. In this article, we provide a comprehensive discussion of the complex mechanisms underlying microvascular inflammation and offer insights into innovative therapeutic strategies that may ameliorate vascular injury in cardiovascular disease. [ABSTRACT FROM AUTHOR]

High-altitude intolerance and consequently high-altitude sickness, is difficult to predict. Liver is an essential organ in glucose and lipid metabolism, and may play key role in the adaptation to high altitude. In response to extreme high altitude, mitochondrial respiration exhibits changes in substrate metabolism, mitochondrial electron transport chain activity, and respiratory coupling. We determined the cobalt chloride (Co[Cl.sub.2]) effects on liver mitochondrial plasticity and oxygen uptake in rats with low resistance (LR) and high resistance (HR) to extreme hypobaric hypoxia. The polarographic method proposed by Chance and Williams was used as a simple and effective tool to trace mitochondrial functionality and oxygen consumption. HR rats had more efficient processes of NADH- and FAD-generated mitochondrial oxidation. Co[Cl.sub.2] promoted more efficient NADH-generated and diminished less efficient FAD-generated mitochondrial respiratory reactions in HR rats. Co[Cl.sub.2] diminished both aerobic and anaerobic processes in LR rats. Glutamate and pyruvate substrates of NADH-generated mitochondrial pathways were highly affected by Co[Cl.sub.2]. Red blood cells acted as cobalt depots in HR and LR rats. We have unveiled several mechanisms leading to differentiated mitochondrial respiratory responses to hypobaric hypoxia in LR and HR rats. Our study strongly supports the existence of adaptive liver mitochondrial plasticity to extreme hypoxia. Key words: hypobaric hypoxia, cobalt chloride, liver mitochondrial respiration, oxidative phosphorylation, anaerobic metabolic pathways. L'intolerance aux hautes altitudes, et consecutivement le mal des montagnes est difficile a predire. Or, le foie est un organe essentiel au metabolisme du glucose et des lipides, et il pourrait jouer un role cle dans l'adaptation aux hautes altitudes. En reaction aux hautes altitudes extremes, la respiration mitochondriale presente des variations dans le metabolisme des substrats, l'activite de la chaine de transport des electrons et le couplage de la respiration. Nous avons etabli les effets du chlorure de cobalt (Co[Cl.sub.2]) sur la plasticite mitochondriale hepatique et la captation de l'oxygene chez des rats presentant une resistance basse (RB) ou elevee (RE) a l'hypoxie hypobare extreme. Nous avons suivi le fonctionnement des mitochondries et la consommation d'oxygene a l'aide de la methode simple et efficace de polarographie mise de l'avant par Chance et Williams. Les rats RE disposaient de processus plus efficaces pour l'oxydation mitochondriale engendree par le NADH et le FAD. Chez les rats HR, le Co[Cl.sub.2] entrainait une amplification des reactions de respiration mitochondriale plus efficaces obtenues avec le NADH et une attenuation des reactions de respiration moins efficaces obtenues avec le FAD. Chez les rats RB, le Co[Cl.sub.2] entrainait une diminution des processus aerobies comme anaerobies. Les substrats glutamate et pyruvate des voies de signalisation mitochondriales portees par le NADH etaient tres affectes par le Co[Cl.sub.2]. Les globules rouges servaient de depots de cobalt chez les rats RE comme RB. Nous avons releve plusieurs modes d'action menant a des reactions differentielles de la respiration mitochondriale a l'hypoxie hypobare chez les rats RE et RB. Notre etude appuie fortement l'existence d'une plasticite mitochondriale hepatique adaptative dans l'hypoxie extreme. [Traduit par la Redaction] Mots-cles : hypoxie hypobare, chlorure de cobalt, respiration mitochondriale hepatique, phosphorylation oxydative, voies metaboliques anaerobies., Introduction In 2018, 2 rescuers from Polish K2 Winter Expedition 2018, Denis Urubko and Adam Bielecki, climbed more than 1000 m up Nanga Parbat, the ninth highest mountain in the [...]

Oxidative stress is involved in the development of various cancers. In the present study, the effect of long-term administration of peroral antidiabetic metformin and pineal hormone melatonin on liver antioxidant and aerobic status in female Sprague-Dawley rats carrying mammary tumors induced by N-methyl-N-nitrosourea was evaluated. Both substances were administered in a preventive and curative manner (12 days before and 16 weeks after the carcinogen application). Carcinogen administration induced oxidative stress: the level of thiobarbituric acid reactive substances (TBARS) considered as a marker of reactive oxygen species (ROS) generation in liver increased as well as the level of oxidatively modified protein content (OMP; aldehyde and ketone derivates). Metformin administration restored succinate dehydrogenase and lactate dehydrogenase activity and associated ROS production and OMP content to the level of intact rats, with predominant activation of superoxide dismutase (SOD) and glutathione reductase (GR). Melatonin alone and in combination with metformin also decreased TBARS content. OMP content decreased in all groups receiving chemoprevention. The rise in total antioxidant capacity after melatonin and particularly metformin and melatonin combination might result from the initiation of anaerobic metabolism and increasing SOD, GR, and glutathione peroxidase activity. Long-term administration of metformin and melatonin exerts antioxidant properties in liver, especially in combination. Key words: metformin, melatonin, liver, high-fat diet, oxidative stress, mammary carcinogenesis. Le stress oxydatif joue un role dans le developpement de divers cancers. Dans la presente etude, nous avons evalue l'effet de l'administration a long terme de metformine (un antidiabetique peroral) et de melatonine (une hormone pineale) sur l'etat d'antioxydation et aerobie du foie chez des rates Sprague-Dawley porteuses de tumeurs mammaires engendrees a l'aide de N-methyl-N-nitrosouree. Les deux substances etaient administrees a visees preventive et curative (12 jours avant et 16 semaines apres l'exposition au carcinogene). L'administration du carcinogene engendrait un stress oxydatif : dans le foie, le taux de substances reagissant a l'acide thiobarbiturique (TBARS pour << thiobarbituric acid reactive substances >>) considerees comme etant un marqueur de la formation de derives reactifs de l'oxygene (ROS pour<>) augmentait tout comme le taux de proteines ayant subi des modifications oxydatives (OMP pour<< oxidatively modified proteins>>: derives aldehydes et cetones). L'administration de metformine permettait de retablir l'activite de la succinate deshydrogenase et de la lactate deshydrogenase, ainsi que la production de ROS associee et les taux d'OMP au niveau de chez des rates intactes, avec l'activation predominante de la superoxyde dismutase (SOD) et de la glutathion reductase (GR). Seule ou en association avec la metformine, la melatonine entramait aussi une diminution des taux de TBARS. Les taux d'OMP s'abaissaient dans tous les groupes recevant une prevention chimiotherapeutique. La hausse de la capacite antioxydante totale apres l'administration de melatonine, et tout particulierement de son association avec la metformine, pourrait provenir de l'entrainement du metabolisme anaerobie et de l'augmentation de l'activite de la SOD, de la GR et de la glutathion peroxydase. L'administration a long terme de metformine et de melatonine exerce des proprietes antioxydantes dans le foie, particulierement en association l'une avec l'autre. [Traduit par la Redaction] Mots-cles: metformine, melatonine, foie, regime alimentaire a teneur elevee en matieres grasses, stress oxydatif, carcinogenese mammaire., Introduction Breast cancer is the most common malignancy globally (Fitzmaurice et al. 2015) and in Europe accounts for 13.5% of all cancer cases (Ferlay et al. 2013). Among many factors, [...]