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Mitochondria are cellular organelles providing energy to the cells. Due to the nature of mitochondrial enzymatic repair systems, mitochondrial DNA tends to generate mutations that are repaired less efficiently than nuclear DNA mutations. There is a certain relationship between the accumulation of mitochondria with mutated DNA in tissues, the development of oxidative stress, and several pathological conditions, from specific mitochondrial diseases to an increased risk of cancer, atherosclerosis, neurodegeneration, and non-systemic inflammation. Mitophagy is the biological mechanism responsible for the degradation of dysfunctional, damaged, and mutant mitochondria. Presumably, the stimulation of mitophagy can lead to tissue cleansing from dysfunctional mitochondria, which can have a powerful therapeutic effect on the root cause of the pathology. This review examines the relationship between mitochondrial mutations and the development of oxidative stress, the mechanisms of mitophagy, and a group of chemicals that stimulate mitophagy. LESS      Full article

Acute coronary syndrome (ACS) disproportionately affects older populations. This is despite advancements in diagnosis and management over the past few decades leading to an overall improvement in clinical outcomes in patients with ACS. Patients aged ≥ 70 years account for more than one third of all patients admitted to hospital with ACS and are at the highest risk of complications including mortality. This article reviews ACS in older populations, including the epidemiology, changes in physiology contributing to increased risk, clinical manifestations, inadequacy of current diagnostic methods, and controversies around recommended management strategies. LESS      Full article

Aim: We evaluated the impact of prior percutaneous coronary intervention (PCI) on early and mid-term results in patients undergoing coronary artery bypass grafting (CABG).Methods: Between 2015 and 2020, 938 consecutive patients (mean age 67.4 ± 9.11 years) underwent CABG with prior PCI (n = 121) or primary CABG (n = 817). The mean follow-up was 37 ± 25 (median 36) months. Kaplan-Meier estimates were used to assess survival rates, while Logistic and Cox model analysis regressions assessed the risk of prior PCI and other variables.Results: Six-year survival including in-hospital mortality was 79% ± 6% in CABG with prior-PCI patients vs.88% ± 2% in primary CABG (P = 0.002). As compared with primary CABG, in prior-PCI patients, clinical presentation (acute coronary syndrome, reduced left ventricular ejection fraction, and previous myocardial infarction, P ≤ 0.01, for all comparisons) was worse, comorbidity increased (Euroscore-2, severe chronic renal dysfunction, P < 0.01), and in-hospital mortality was higher (6.6% or 8 patients vs. 1.6% or 13 patients, P < 0.001). Prior PCI was found to be an independent predictor of mortality (HR = 4.23; P = 0.01). Six-year freedom from late all-cause death and cardiac death were 84% ± 6% vs. 90% ± 2% (P = 0.2) and 96% ± 2% vs. 96% ± 1% (P = 0.5), respectively. Independent predictors of all-cause death were advanced age at the operation (P < 0.0001), reduced left ventricular ejection fraction (P = 0.01), severe chronic renal dysfunction (P = 0.02), prior PCI (P = 0.03), and Euroscore-2 (P = 0.05). Prior PCI did not negatively affect late cardiac death (P = 0.5).Conclusion: Patients undergoing CABG after prior PCI have worse perioperative outcomes. Mid-term reduced survival in the prior-PCI patients is mainly due to the concomitant presence of worse clinical presentation and increased comorbidity. Freedom from cardiac death is comparable and satisfactory in both cohorts, highlighting the positive protective effect of CABG over time. LESS      Full article

The periprocedural management of anticoagulation in patients who require non-cardiac surgery is a common clinical problem due to the aging of the population associated with both an increase in the use of anticoagulants and a higher need for surgery. If surgery is needed in a patient on anticoagulant therapy, regardless of the drug used, it is necessary to consider the urgency of the surgical procedure and the balance between the thromboembolic risk related to the discontinuation of therapy and the hemorrhagic risk related to the surgical procedure itself. Finally, a topic still much discussed that derives from the combined evaluation of these factors is the possible indication of a bridge therapy (“bridging anticoagulation”) to limit the thromboembolic risk related to the discontinuation of treatment. The different strategies in patients under antivitamin K and direct oral anticoagulants are reviewed. LESS      Full article

Amyloid light-chain (AL) amyloidosis is the most common type of systemic amyloidosis and is a multi-organ disease affecting mostly the heart and kidneys. AL amyloidosis is a protein misfolding disorder characterized by the tissue deposition of monoclonal light chains (LCs) produced by neoplastic plasma cells. Measurement of circulating free LC (FLC) is an important tool for diagnosis, risk stratification, and management of AL amyloidosis and can be performed through antibody-based methods or mass spectrometry. Furthermore, correct identification of LC deposits in tissues is essential to diagnose AL amyloidosis. Together with antibody-based techniques, methods relying on mass spectroscopy are now available. LESS      Full article

Mitochondria do not exist as separate formations in the cell; they form a homogeneous network in which the processes of division and fusion continuously occur. A shift in this balance, as well as mitochondrial dysfunction, leads to the development of chronic and metabolic disorders. Metabolic changes in mitochondria control the formation and differentiation of monocytes. Pro-inflammatory activation of monocytes/macrophages leads to a decrease in oxidative phosphorylation and an increase in mitochondrial fusion. To date, the molecular mechanisms that regulate mitochondrial dynamics to control life and death in monocytes are not well understood. In addition, there is ample evidence that abnormal mitochondrial metabolism is involved in the pathogenesis of many diseases. Mitochondrial stress and damage contribute to cell death, metabolic disorders, and inflammation. In this review, we consider in detail the involvement of mitochondrial processes in the development of pathologies and discuss how mitochondria can be therapeutically affected. Attention is also drawn to possible diagnostic studies that target mitochondrial dynamics of disorders in monocytes. LESS      Full article

Utilization of contrast media to visualize vasculature structures in the setting of cardiovascular disorders (CVD) can lead to acute kidney injury, referred to as contrast-induced nephropathy (CIN). CIN can potentiate mortality and hospitalization in aged individuals, patients with CVD, nephropathy, enhancing kidney damage, and cardiac events. Preventing CIN by identifying risk factors is important. The underlying mechanisms of CIN pathology are unclear, but the key factors include direct cytotoxicity, oxidative stress, vascular and endothelial dysfunction and inflammatory processes. Reactive Oxygen Species and inflammatory mediators have been proposed as key factors influencing the development of CIN and CVD, and the elucidation of the interplay between the mechanisms evoked by them may provide a better understanding of the signaling processes happening in these conditions, thereby potentially enabling early identification, prevention and characterization of novel drug targets. LESS      Full article

The role of exosomes in different physiological and pathological settings is an emerging field of great current interest. One hallmark of exosomes is the promotion of blood vessel formation. Exosomes of different cellular origin have been shown to be enriched in angiogenic proteins which directly promote angiogenesis. In addition, exosomes are also efficacious producers of adenosine and potentially encapsulate adenosine in their lumen. The adenosine content of exosomes has been linked to their immunosuppressive effects. In this communication, we consider the possibility that adenosine production by tumor cell-derived exosomes may represent a novel pathway for stimulation of angiogenesis in the tumor microenvironment. LESS      Full article

Atherosclerosis is the main pathological basis of most cardiovascular diseases and the leading health threat in the world. Of note, lipid-lowering therapy cannot completely retard atherosclerosis progression, even in patients treated with combined statins and PCSK9 inhibitors. This failure further impels researchers to explore other underlying therapeutic strategies except for lipid-lowering. Monocytes and macrophages are the major immune cell groups in atherosclerotic plaques. They play important roles in all stages of atherosclerosis, including the occurrence, advance, and regression. It is interesting that macrophages are demonstrated to have plastic and heterogenous characteristics within the dynamic atherosclerotic plaque microenvironment. Furthermore, the phenotype of macrophages can switch upon different microenvironmental stimulus. Therefore, macrophages have become a potential therapeutic target for anti-atherosclerosis treatment. This article reviews the phenotypic diversity of macrophages and their roles in dynamic atherosclerotic plaque microenvironment, especially the related signaling pathways involved in macrophage polarization and compounds exhibiting therapeutic effects. LESS      Full article

The vascular endothelium is a vital component in maintaining the structure and function of blood vessels. The endothelial cells (ECs) mediate vital regulatory functions such as the proliferation of cells, permeability of various tissue membranes, and exchange of gases, thrombolysis, blood flow, and homeostasis. The vascular endothelium also regulates inflammation and immune cell trafficking, and ECs serve as a replicative niche for many bacterial, viral, and protozoan infectious diseases. Endothelial dysfunction can lead to vasodilation and pro-inflammation, which are the hallmarks of many severe diseases. Exosomes are nanoscale membrane-bound vesicles that emerge from cells and serve as important extracellular components, which facilitate communication between cells and maintain homeostasis during normal and pathophysiological states. Exosomes are also involved in gene transfer, inflammation and antigen presentation, and mediation of the immune response during pathogenic states. Protozoa are a diverse group of unicellular organisms that cause many infectious diseases in humans. In this regard, it is becoming increasingly evident that many protozoan parasites (such as Plasmodium, Trypanosoma, Leishmania, and Toxoplasma) utilize exosomes for the transfer of their virulence factors and effector molecules into the host cells, which manipulate the host gene expression, immune responses, and other biological activities to establish and modulate infection. In this review, we discuss the role of the vascular endothelium and exosomes in and their contribution to pathogenesis in malaria, African sleeping sickness, Chagas disease, and leishmaniasis and toxoplasmosis with an emphasis on their actions on the innate and adaptive immune mechanisms of resistance. LESS      Full article