scholarly journals Part One: Extracellular Vesicles as Valuable Players in Diabetic Cardiovascular Diseases

Author(s):  
Mihaela Gherghiceanu ◽  
Nicoleta Alexandru ◽  
Stefania Lucia Magda ◽  
Alina Constantin ◽  
Miruna Nemecz ◽  
...  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anna Lebedeva ◽  
Wendy Fitzgerald ◽  
Ivan Molodtsov ◽  
Alexander Shpektor ◽  
Elena Vasilieva ◽  
...  

AbstractA proinflammatory dysregulation of cytokine release is associated with various diseases, in particular with those of infectious etiology, as well as with cardiovascular diseases (CVD). We showed earlier that cytokines are released in two forms, soluble and in association with extracellular vesicles (EVs). Here, we investigated the patterns of expression and clustering of soluble and EV-associated cytokines in patients with ST-elevation myocardial infarction (STEMI). We collected plasma samples from 48 volunteers without CVD and 62 patients with STEMI, separated soluble and EV fractions, and analyzed them for 33 cytokines using a multiplexed bead-based assay. We identified soluble and EV-associated cytokines that are upregulated in STEMI and form correlative clusters. Several clustered soluble cytokines were expressed almost exclusively in patients with STEMI. EV-associated cytokines were largely not affected by STEMI, except for pro-inflammatory cytokines IL-6, IL-18, and MIG, as well as anti-inflammatory IL-2 that were upregulated in a correlated fashion. Our results demonstrated that soluble cytokines in patients with STEMI are upregulated in a coordinated fashion in contrast to the mainly unaffected system of EV-associated cytokines. Identification of cytokine clusters affected differently by STEMI now permits investigation of their differential contributions to this pathology.


2019 ◽  
Vol 125 (9) ◽  
pp. 805-820 ◽  
Author(s):  
Sarvesh Chelvanambi ◽  
Samir K. Gupta ◽  
Xingjuan Chen ◽  
Bradley W. Ellis ◽  
Bernhard F. Maier ◽  
...  

Rationale: Even in antiretroviral therapy-treated patients, HIV continues to play a pathogenic role in cardiovascular diseases. A possible cofactor may be persistence of the early HIV response gene Nef, which we have demonstrated recently to persist in the lungs of HIV+ patients on antiretroviral therapy. Previously, we have reported that HIV strains with Nef, but not Nef-deleted HIV strains, cause endothelial proinflammatory activation and apoptosis. Objective: To characterize mechanisms through which HIV-Nef leads to the development of cardiovascular diseases using ex vivo tissue culture approaches as well as interventional experiments in transgenic murine models. Methods and Results: Extracellular vesicles derived from both peripheral blood mononuclear cells and plasma from HIV+ patient blood samples induced human coronary artery endothelial cells dysfunction. Plasma-derived extracellular vesicles from antiretroviral therapy+ patients who were HIV-Nef+ induced significantly greater endothelial apoptosis compared with HIV-Nef-plasma extracellular vesicles. Both HIV-Nef expressing T cells and HIV-Nef-induced extracellular vesicles increased transfer of cytosol and Nef protein to endothelial monolayers in a Rac1-dependent manner, consequently leading to endothelial adhesion protein upregulation and apoptosis. HIV-Nef induced Rac1 activation also led to dsDNA breaks in endothelial colony forming cells, thereby resulting in endothelial colony forming cell premature senescence and endothelial nitric oxide synthase downregulation. These Rac1-dependent activities were characterized by NOX2-mediated reactive oxygen species production. Statin treatment equally inhibited Rac1 inhibition in preventing or reversing all HIV-Nef-induction abnormalities assessed. This was likely because of the ability of statins to block Rac1 prenylation as geranylgeranyl transferase inhibitors were effective in inhibiting HIV-Nef-induced reactive oxygen species formation. Finally, transgenic expression of HIV-Nef in endothelial cells in a murine model impaired endothelium-mediated aortic ring dilation, which was then reversed by 3-week treatment with 5 mg/kg atorvastatin. Conclusions: These studies establish a mechanism by which HIV-Nef persistence despite antiretroviral therapy could contribute to ongoing HIV-related vascular dysfunction, which may then be ameliorated by statin treatment.


2019 ◽  
Vol 20 (13) ◽  
pp. 3272 ◽  
Author(s):  
Suet Yen Chong ◽  
Choon Keong Lee ◽  
Chenyuan Huang ◽  
Yi Hsuan Ou ◽  
Christopher J. Charles ◽  
...  

Cardiovascular diseases (CVD) represent the leading cause of morbidity and mortality globally. The emerging role of extracellular vesicles (EVs) in intercellular communication has stimulated renewed interest in exploring the potential application of EVs as tools for diagnosis, prognosis, and therapy in CVD. The ubiquitous nature of EVs in biological fluids presents a technological advantage compared to current diagnostic tools by virtue of their notable stability. EV contents, such as proteins and microRNAs, represent specific signatures of cellular activation or injury. This feature positions EVs as an alternative source of biomarkers. Furthermore, their intrinsic activity and immunomodulatory properties offer EVs unique opportunities to act as therapeutic agents per se or to serve as drug delivery carriers by acting as miniaturized vehicles incorporating bioactive molecules. In this article, we aim to review the recent advances and applications of EV-based biomarkers and therapeutics. In addition, the potential of EVs as a drug delivery and theranostic platform for CVD will also be discussed.


Lab on a Chip ◽  
2018 ◽  
Vol 18 (19) ◽  
pp. 2917-2925 ◽  
Author(s):  
Hong-Lin Cheng ◽  
Chien-Yu Fu ◽  
Wen-Che Kuo ◽  
Yen-Wen Chen ◽  
Yi-Sin Chen ◽  
...  

A novel microfluidic platform for extracellular vesicle extraction, microRNA isolation and detection with field-effect transistors for early detection of cardiovascular diseases.


Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 843 ◽  
Author(s):  
Alice Mallia ◽  
Erica Gianazza ◽  
Beatrice Zoanni ◽  
Maura Brioschi ◽  
Silvia Stella Barbieri ◽  
...  

Extracellular vesicles (EVs) are lipid-bound vesicles released from cells under physiological and pathological conditions. Basing on biogenesis, dimension, content and route of secretion, they can be classified into exosomes, microvesicles (MVs) and apoptotic bodies. EVs have a key role as bioactive mediators in intercellular communication, but they are also involved in other physiological processes like immune response, blood coagulation, and tissue repair. The interest in studying EVs has increased over the years due to their involvement in several diseases, such as cardiovascular diseases (CVDs), and their potential role as biomarkers in diagnosis, therapy, and in drug delivery system development. Nowadays, the improvement of mass spectrometry (MS)-based techniques allows the characterization of the EV protein composition to deeply understand their role in several diseases. In this review, a critical overview is provided on the EV’s origin and physical properties, as well as their emerging functional role in both physiological and disease conditions, focusing attention on the role of exosomes in CVDs. The most important cardiac exosome proteomic studies will be discussed giving a qualitative and quantitative characterization of the exosomal proteins that could be used in future as new potential diagnostic markers or targets for specific therapies.


Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 388
Author(s):  
Renata Caroline Costa de Freitas ◽  
Rosario Dominguez Crespo Hirata ◽  
Mario Hiroyuki Hirata ◽  
Elena Aikawa

Extracellular vesicles (EVs) are composed of a lipid bilayer containing transmembrane and soluble proteins. Subtypes of EVs include ectosomes (microparticles/microvesicles), exosomes, and apoptotic bodies that can be released by various tissues into biological fluids. EV cargo can modulate physiological and pathological processes in recipient cells through near- and long-distance intercellular communication. Recent studies have shown that origin, amount, and internal cargos (nucleic acids, proteins, and lipids) of EVs are variable under different pathological conditions, including cardiovascular diseases (CVD). The early detection and management of CVD reduce premature morbidity and mortality. Circulating EVs have attracted great interest as a potential biomarker for diagnostics and follow-up of CVD. This review highlights the role of circulating EVs as biomarkers for diagnosis, prognosis, and therapeutic follow-up of CVD, and also for drug delivery. Despite the great potential of EVs as a tool to study the pathophysiology of CVD, further studies are needed to increase the spectrum of EV-associated applications.


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Shihui Fu ◽  
Yujie Zhang ◽  
Yulong Li ◽  
Leiming Luo ◽  
Yali Zhao ◽  
...  

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