Obesity is associated with increased cardiovascular disease. Metabolic syndrome (MS) identifies substantial additional cardiovascular risk beyond the individual risk factors, and is a powerful predictor of cardiovascular events even regardless of body mass index, thus suggesting a common downstream pathway conferring increased cardiovascular risk. Platelet hyper-reactivity/activation plays a central role to accelerate atherothrombosis and is the result of the interaction among the features clustering in obesity and MS: insulin resistance, inflammation, oxidative stress, endothelial dysfunction. Interestingly, the same pathogenic events largely account for the less-than-expected response to antiplatelet agents, namely low-dose aspirin. The proposed explanations for this phenomenon, besides underdosing of drug and/or reduced bioavailability, subsequent to excess of adipose tissue, include enhanced platelet turnover, leading to unacetylated COX-1 and COX-2 in newly formed platelets as a source of aspirin-escaping thromboxane formation; extraplatelet sources of thromboxane, driven by inflammatory triggers; and enhanced lipid peroxidation, activating platelets with a mechanism bypassing COX-1 acetylation or limiting COX-isozyme acetylation by aspirin. This review will address the complex interactions between platelets and the pathogenic events occurring in obesity and MS, trying to translate this body of mechanistic information into a clinically relevant read-out, in order to establish novel strategies in the prevention/treatment of atherothrombosis.
Extracellular vesicles act as shuttle vectors or signal transducers that can deliver specific biological information and have progressively emerged as key regulators of organized communities of cells within multicellular organisms in health and disease. Here, we survey the evolutionary origin, general characteristics, and biological significance of extracellular vesicles as mediators of intercellular signaling, discuss the various subtypes of extracellular vesicles thus far described and the principal methodological approaches to their study, and review the role of extracellular vesicles in tumorigenesis, immunity, non-synaptic neural communication, vascular-neural communication through the blood-brain barrier, renal pathophysiology, and embryo-fetal/maternal communication through the placenta.
The renin-angiotensin system (RAS) plays a main role in regulating blood pressure and electrolyte and liquid balance. Previous evidence suggests that RAS may represent an important target for the treatment of lung pathologies, especially for acute respiratory distress syndrome and chronic fibrotic disease. The scientific community has recently focused its attention on angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor 1 (AT1R) inhibitors and their possible benefit/harms for patients infected by Coronavirus disease (COVID-19) who experience pneumonia, but there are still some doubts about the effects of these drugs in this setting.
Android obesity is associated with enhanced lipid peroxidation and persistent platelet activation. These abnormalities are driven by inflammatory triggers related to the degree of abdominal adiposity and are, at least in part, reversible with a successful weight-loss program.
Android obesity is associated with a concomitant reduction of IL-10 and adiponectin levels. However, the antiinflammatory status of obesity might require prolonged periods of energy-restricted diets to revert to normal.
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