scholarly journals Extracellular Vesicles in Comorbidities Associated with Ischaemic Heart Disease: Focus on Sex, an Overlooked Factor

2021 ◽  
Vol 10 (2) ◽  
pp. 327
Author(s):  
Claudia Penna ◽  
Saveria Femminò ◽  
Giuseppe Alloatti ◽  
Maria F. Brizzi ◽  
Tommaso Angelone ◽  
...  
Keyword(s):  
Sex Differences ◽  
Extracellular Vesicles ◽  
Personalised Medicine ◽  
Myocardial Damage ◽  
Ischaemia Reperfusion Injury ◽  
Early Markers ◽  
Ischemic Diseases ◽  
Reduce Risk ◽  
Therapeutic Tools ◽  
Disease Focus

Extracellular vesicles (EV) are emerging early markers of myocardial damage and key mediators of cardioprotection. Therefore, EV are becoming fascinating tools to prevent cardiovascular disease and feasible weapons to limit ischaemia/reperfusion injury. It is well known that metabolic syndrome negatively affects vascular and endothelial function, thus creating predisposition to ischemic diseases. Additionally, sex is known to significantly impact myocardial injury and cardioprotection. Therefore, actions able to reduce risk factors related to comorbidities in ischaemic diseases are required to prevent maladaptive ventricular remodelling, preserve cardiac function, and prevent the onset of heart failure. This implies that early diagnosis and personalised medicine, also related to sex differences, are mandatory for primary or secondary prevention. Here, we report the contribution of EV as biomarkers and/or therapeutic tools in comorbidities predisposing to cardiac ischaemic disease. Whenever possible, attention is dedicated to data linking EV to sex differences.

scholarly journals Obesity and hypertensive heart disease: focus on body composition and sex differences

2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Giovanni de Simone ◽  
Costantino Mancusi ◽  
Raffaele Izzo ◽  
Maria Angela Losi ◽  
L. Aldo Ferrara
Keyword(s):  
Body Composition ◽  
Sex Differences ◽  
Heart Disease ◽  
Hypertensive Heart Disease ◽  
Disease Focus

scholarly journals Early podocyte injury and elevated levels of urinary podocyte-derived extracellular vesicles in swine with metabolic syndrome: role of podocyte mitochondria

2019 ◽  
Vol 317 (1) ◽  
pp. F12-F22 ◽  
Author(s):  
Li-Hong Zhang ◽  
Xiang-Yang Zhu ◽  
Alfonso Eirin ◽  
Arash Aghajani Nargesi ◽  
John R. Woollard ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Extracellular Vesicles ◽  
Light And Electron Microscopy ◽  
Urinary Concentration ◽  
Glomerular Injury ◽  
Podocyte Injury ◽  
Early Markers ◽  
Nutrient Surplus ◽  
Glomerular Size ◽  
Foot Process

Metabolic syndrome (MetS) is associated with nutrient surplus and kidney hyperfiltration, accelerating chronic renal failure. The potential involvement of podocyte damage in early MetS remains unclear. Mitochondrial dysfunction is an important determinant of renal damage, but whether it contributes to MetS-related podocyte injury remains unknown. Domestic pigs were studied after 16 wk of diet-induced MetS, MetS treated with the mitochondria-targeted peptide elamipretide (ELAM; 0.1 mg·kg−1·day−1 sc) for the last month of diet, and lean controls ( n = 6 pigs/group). Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured using multidetector computed tomography, and podocyte and mitochondrial injury were measured by light and electron microscopy. Urinary levels of podocyte-derived extracellular vesicles (pEVs; nephrin positive/podocalyxin positive) were characterized by flow cytometry. Body weight, blood pressure, RBF, and GFR were elevated in MetS. Glomerular size and glomerular injury score were also elevated in MetS and decreased after ELAM treatment. Evidence of podocyte injury, impaired podocyte mitochondria, and foot process width were all increased in MetS but restored with ELAM. The urinary concentration of pEVs was elevated in MetS pigs and directly correlated with renal dysfunction, glomerular injury, and fibrosis and inversely correlated with glomerular nephrin expression. Additionally, pEV numbers were elevated in the urine of obese compared with lean human patients. Early MetS induces podocyte injury and mitochondrial damage, which can be blunted by mitoprotection. Urinary pEVs reflecting podocyte injury might represent early markers of MetS-related kidney disease and a novel therapeutic target.

An Introduction to Cardioprotection

2011 ◽  
Keyword(s):  
Reperfusion Injury ◽  
Myocardial Injury ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Myocardial Damage ◽  
Myocardial Salvage ◽  
Ischaemia Reperfusion Injury ◽  
Acute Ischaemia ◽  
Ischaemia Reperfusion ◽  
Considerable Morbidity

• In its broadest sense, the term ‘cardioprotection’ encompasses ‘all mechanisms and means that contribute to the preservation of the heart by reducing or even preventing myocardial damage’• However, for the purposes of this book, the term ‘cardioprotection’ will refer to the endogenous mechanisms and therapeutic strategies that reduce or prevent myocardial damage induced by acute ischaemia-reperfusion injury• In this context, cardioprotection begins with the primary prevention of coronary heart disease and includes the reduction of myocardial injury sustained during coronary artery bypass graft surgery, and an acute myocardial infarction, conditions with considerable morbidity and mortality• An understanding of the pathophysiology of acute myocardial ischaemia-reperfusion injury is essential when designing new cardioprotective strategies• Several methods exist for both quantifying myocardial damage induced by acute ischaemia-reperfusion injury and for assessing myocardial salvage following the application of cardioprotective strategies• Importantly, novel cardioprotective strategies must be capable of preventing and reducing myocardial damage over and above that provided by current optimal therapy.

scholarly journals Mesenchymal stromal cells and their secreted extracellular vesicles as therapeutic tools for COVID-19 pneumonia?

2020 ◽  
Vol 325 ◽  
pp. 135-140 ◽  
Author(s):  
Maurizio Muraca ◽  
Augusto Pessina ◽  
Michela Pozzobon ◽  
Massimo Dominici ◽  
Umberto Galderisi ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Tools

scholarly journals Why the need and how to approach the functional diversity of extracellular vesicles

2017 ◽  
Vol 373 (1737) ◽  
pp. 20160479 ◽  
Author(s):  
Mercedes Tkach ◽  
Joanna Kowal ◽  
Clotilde Théry
Keyword(s):  
Plasma Membrane ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Tumour Microenvironment ◽  
Efficient Separation ◽  
The Past ◽  
Therapeutic Tools ◽  
Opinion Article ◽  
Current Stage

In the past decade, cell-to-cell communication mediated by exosomes has attracted growing attention from biomedical scientists and physicians, leading to several recent publications in top-tier journals. Exosomes are generally defined as secreted membrane vesicles, or extracellular vesicles (EVs), corresponding to the intraluminal vesicles of late endosomal compartments, which are secreted upon fusion of multi-vesicular endosomes with the cell's plasma membrane. Cells, however, were shown to release other types of EVs, for instance, by direct budding off their plasma membrane. Some of these EVs share with exosomes major biophysical and biochemical characteristics, such as size, density and membrane orientation, which impose difficulties in their efficient separation. Despite frequent claims in the literature, whether exosomes really display more important patho/physiological functions, or are endowed with higher potential as diagnostic or therapeutic tools than other EVs, is not yet convincingly demonstrated. In this opinion article, we describe reasons for this lack of precision knowledge in the current stage of the EV field, we review recently described approaches to overcome these caveats, and we propose ways to improve our knowledge on the respective functions of distinct EVs, which will be crucial for future development of well-designed EV-based clinical applications. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

scholarly journals Sex-differences in circulating biomarkers during acute myocardial infarction: An analysis from the SWEDEHEART registry

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249830
Author(s):  
Kai M. Eggers ◽  
Lars Lindhagen ◽  
Tomasz Baron ◽  
David Erlinge ◽  
Marcus Hjort ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Sex Differences ◽  
Multiple Testing ◽  
Plaque Rupture ◽  
Multiple Reaction Monitoring ◽  
Myocardial Necrosis ◽  
Myocardial Damage ◽  
Circulating Biomarkers ◽  
High Discrimination ◽  
Penalized Logistic Regression

Background Sex-differences in the pathobiology of myocardial infarction are well established but incompletely understood. Improved knowledge on this topic may help clinicians to improve management of men and women with myocardial infarction. Methods In this registry-based cohort study (SWEDEHEART), we analyzed 175 circulating biomarkers reflecting various pathobiological axes in 856 men and 243 women admitted to Swedish coronary care units because of myocardial infarction. Two multimarker panels were applied (Proximity Extension Assay [Olink Bioscience], Multiple Reaction Monitoring mass spectrometry). Lasso analysis (penalized logistic regression), multiple testing-corrected Mann-Whitney tests and Cox regressions were used to assess sex-differences in the concentrations of these biomarkers and their implications on all-cause mortality and major adverse events (median follow-up up to 6.6 years). Results Biomarkers provided a very high discrimination between both sexes, when considered simultaneously (c-statistics 0.972). Compared to women, men had higher concentrations of six biomarkers with the most pronounced differences seen for those reflecting atherogenesis, myocardial necrosis and metabolism. Women had higher concentrations of 14 biomarkers with the most pronounced differences seen for those reflecting activation of the renin-angiotensin-aldosterone axis, inflammation and for adipokines. There were no major variations between sexes in the associations of these biomarkers with outcome. Conclusions Severable sex-differences exist in the expression of biomarkers in patients with myocardial infarction. While these differences had no impact on outcome, our data suggest the presence of various sex-related pathways involved in the development of coronary atherosclerosis, the progression to plaque rupture and acute myocardial damage, with a greater heterogeneity in women.

scholarly journals Extracellular Vesicles: Novel Roles in Neurological Disorders

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Qian Jin ◽  
Peipei Wu ◽  
Xinru Zhou ◽  
Hui Qian ◽  
Wenrong Xu
Keyword(s):  
Central Nervous System ◽  
Extracellular Vesicles ◽  
Neurological Disorders ◽  
Unique Feature ◽  
Cns Development ◽  
Diagnostic Biomarkers ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Therapeutic Tools ◽  
Almost All

Exosomes are small extracellular vesicles (EVs) secreted by almost all cells, which have been recognized as a novel platform for intercellular communication in the central nervous system (CNS). Exosomes are capable of transferring proteins, nucleic acids, lipids, and metabolites between neurons and glial cells, contributing to CNS development and maintenance of homeostasis. Evidence shows that exosomes originating from CNS cells act as suppressors or promoters in the initiation and progression of neurological disorders. Moreover, these exosomes have been shown to transfer molecules associated with diseases through the blood-brain barrier (BBB) and thus can be detected in blood. This unique feature enables exosomes to act as potential diagnostic biomarkers for neurological disorders. In addition, a substantial number of researches have indicated that exosomes derived from mesenchymal stem cells (MSCs) have repair effects on neurological disorders. Herein, we briefly introduce the roles of exosomes under physiological and pathological conditions. In particular, novel roles of exosomes as potential diagnostic biomarkers and therapeutic tools for neurological disorders are highlighted.

scholarly journals Advances in the Field of Micro- and Nanotechnologies Applied to Extracellular Vesicle Research: Take-Home Message from ISEV2021

Micromachines ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1563
Author(s):  
Silvia Picciolini ◽  
Francesca Rodà ◽  
Marzia Bedoni ◽  
Alice Gualerzi
Keyword(s):  
Annual Meeting ◽  
Extracellular Vesicles ◽  
International Society ◽  
Biomedical Research ◽  
Human Body ◽  
Knowledge Exchange ◽  
Extracellular Vesicle ◽  
Present Review ◽  
Knowledge Gaps ◽  
Therapeutic Tools

Extracellular Vesicles (EVs) are naturally secreted nanoparticles with a plethora of functions in the human body and remarkable potential as diagnostic and therapeutic tools. Starting from their discovery, EV nanoscale dimensions have hampered and slowed new discoveries in the field, sometimes generating confusion and controversies among experts. Microtechnological and especially nanotechnological advances have sped up biomedical research dealing with EVs, but efforts are needed to further clarify doubts and knowledge gaps. In the present review, we summarize some of the most interesting data presented in the Annual Meeting of the International Society for Extracellular Vesicles (ISEV), ISEV2021, to stimulate discussion and to share knowledge with experts from all fields of research. Indeed, EV research requires a multidisciplinary knowledge exchange and effort. EVs have demonstrated their importance and significant biological role; still, further technological achievements are crucial to avoid artifacts and misleading conclusions in order to enable outstanding discoveries.

An Emerging Fluorescence-Based Technique for Quantification and Protein Profiling of Extracellular Vesicles

2020 ◽  
pp. 247263032097045
Author(s):  
Mehdi Dehghani ◽  
Rebecca K. Montange ◽  
Michael W. Olszowy ◽  
David Pollard
Keyword(s):  
Flow Cytometry ◽  
Extracellular Vesicles ◽  
Protein Profiling ◽  
Submicron Particles ◽  
Protein Markers ◽  
Bulk Analysis ◽  
Precise Quantification ◽  
Therapeutic Tools ◽  
Different Sources

Robust and well-established techniques for the quantification and characterization of extracellular vesicles (EVs) are a crucial need for the utilization of EVs as potential diagnostic and therapeutic tools. Current bulk analysis techniques such as proteomics and Western blot suffer from low resolution in the detection of small changes in target marker expression levels, exemplified by the heterogeneity of EVs. Microscopy-based techniques can provide valuable information from individual EVs; however, they are time-consuming and statistically less powerful than other techniques. Flow cytometry has been successfully employed for the quantification and characterization of individual EVs within larger populations. However, traditional flow cytometry is not highly suited for the examination of smaller, submicron particles. Here we demonstrate the accurate and precise quantification of nanoparticles such as EVs using the Virus Counter 3100 (VC3100) platform, a fluorescence-based technique that uses the principles of flow cytometry with critical enhancements to enable the effective detection of smaller particles. This approach can detect nanoparticles precisely with no evidence of inaccurate concentration measurement from masking effects associated with traditional nanoparticle tracking analysis (NTA). Fluorescently labeled EVs from different sources were successfully quantified using the VC3100 without a postlabeling washing step. Moreover, protein profiling and characterization of individual EVs were achieved and have been shown to determine the expression level of target protein markers.

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