Red Blood Cells and Endothelium Derived Circulating Extracellular Vesicles in Health and Chronic Heart Failure: A Focus on Phosphatidylserine Dynamics in Vesiculation DOI Open Access
Rosa Suades, Alba Vilella-Figuerola, Teresa Padró

et al.

Published: June 30, 2023

Circulating extracellular microvesicles (cEVs) are characterised by presenting surface antigens of parental cells. Since their biogenesis involves the translocation phosphatidylserine (PS) from inner to outer-leaflet plasma membrane, exposed PS has been considered as a recognition hallmark cEVs. However, not all cEVs externalise PS. In this study we have phenotypically and quantitatively flow cytometry with special attention proportions in chronic heart failure patients (cHF; n=119) reference non-HF group (n=21). PS─-cEVs were predominantly found both groups. Parental markers showed differential pattern depending on exposure. Endothelium-derived connexin 43-rich mainly significantly increased cHF. On contrary, platelet-derived mostly PS+ non-HF. We observed similar levels PS+- subjects when analysing immune cell-derived EVs, but there was subset-specific difference cHF patients. Indeed, those carrying CD45+, CD29+, CD11b+ CD15+ PS+-cEVs, while CD14+, CD3+ CD56+ PS─-cEVs. conclusion, endothelial red blood cells stressed detected high shedding Despite PS+-cEVs represent two distinct cEV populations, release potential function biomarkers shuttles for cell communication seem unrelated content.

Language: Английский

Lipoprotein(a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment DOI Creative Commons
Stamatios Lampsas,

Maria Xenou,

Evangelos Oikonomou

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(3), P. 969 - 969

Published: Jan. 18, 2023

Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a). Increased Lp(a) levels are an independent, heritable causal risk factor for atherosclerotic cardiovascular disease (ASCVD) as they largely determined by variations in the gene (LPA) locus encoding apo(a). preferential carrier oxidized phospholipids (OxPL), and its role adversely affects vascular inflammation, lesions, endothelial function thrombogenicity, which pathophysiologically leads (CV) events. Despite this crucial of Lp(a), measurement lacks globally unified method, and, between different laboratories, results need standardization. Standard antilipidemic therapies, such statins, fibrates ezetimibe, have mediocre effect on levels, although it not yet clear whether treatments can affect CV events prognosis. This narrative review aims summarize knowledge regarding mechanisms mediating atherosclerosis thrombosis discuss current diagnostic therapeutic potentials.

Language: Английский

Citations

69
Understanding the intricacies of cellular senescence in atherosclerosis: Mechanisms and therapeutic implications DOI Creative Commons
Ilyas Ali, Hongliang Zhang, Syed Aqib Ali Zaidi

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102273 - 102273

Published: March 14, 2024

Language: Английский

Citations

11
Extracellular vesicles in atherothrombosis: From biomarkers and precision medicine to therapeutic targets DOI
Lina Badimón, Teresa Padró, Gemma Arderiu

et al.

Immunological Reviews, Journal Year: 2022, Volume and Issue: 312(1), P. 6 - 19

Published: Aug. 22, 2022

Summary Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of global mortality. Extracellular vesicles (EVs) are small phospholipid that convey molecular bioactive cargoes and play essential roles in intercellular communication and, hence, a multifaceted role health disease. The present review offers glimpse into current state up‐to‐date concepts on EV field. It also covers their association with several risk factors ischemic conditions, being subclinical atherosclerosis utmost relevance for prevention. Interestingly, we show EVs hold promise as prognostic diagnostic well predictive markers ASCVD precision medicine era. We then report atherothrombosis, disentangling mechanisms involved initiation, progression, complication showing direct effect context arterial thrombosis. Finally, potential use therapeutic intervention is highlighted.

Language: Английский

Citations

35
Pollution from fine particulate matter and atherosclerosis: A narrative review DOI Creative Commons
Chiara Macchi, Cesare R. Sirtori, Alberto Corsini

et al.

Environment International, Journal Year: 2023, Volume and Issue: 175, P. 107923 - 107923

Published: April 10, 2023

According to the WHO, entire global population is exposed air pollution levels higher than recommended for health preservation. Air a complex mixture of nano- micro-sized particles and gaseous components that poses major threat public health. Among most important pollutants, causal associations have been established between particulate matter (PM), mainly < 2.5 μm, cardiovascular diseases (CVD), i.e., hypertension, coronary artery disease, ischemic stroke, congestive heart failure, arrhythmias as well total mortality. Aim this narrative review describe critically discuss proatherogenic effects PM2.5 attributed many direct or indirect comprising endothelial dysfunction, chronic low-grade inflammatory state, increased production reactive oxygen species, mitochondrial dysfunction activation metalloproteases, all leading unstable arterial plaques. Higher concentrations pollutants are associated with presence vulnerable plaques plaque ruptures witnessing instability. often disregarded CVD risk factor, in spite fact it one main modifiable factors relevant prevention management CVD. Thus, not only structural actions should be taken order mitigate emissions, but professionals also take care counsel patients on risks pollution.

Language: Английский

Citations

22
Optimized operation of a controlled stirred tank reactor system for the production of mesenchymal stromal cells and their extracellular vesicles DOI
Ana Fernandes‐Platzgummer, Raquel Cunha, Sara Morini

et al.

Biotechnology and Bioengineering, Journal Year: 2023, Volume and Issue: 120(9), P. 2742 - 2755

Published: June 15, 2023

Abstract The therapeutic effects of human mesenchymal stromal cells (MSC) have been attributed mostly to their paracrine activity, exerted through small‐secreted extracellular vesicles (EVs) rather than engraftment into injured tissues. Currently, the production MSC‐derived EVs (MSC‐EVs) is performed in laborious static culture systems with limited manufacturing capacity using serum‐containing media. In this work, a serum‐/xenogeneic‐free microcarrier‐based system was successfully established for bone marrow‐derived MSC cultivation and MSC‐EV 2 l ‐scale controlled stirred tank reactor (STR) operated under fed‐batch (FB) or combined continuous perfusion (FB/CP). Overall, maximal cell numbers (3.0 ± 0.12) × 10 8 (5.3 0.32) were attained at Days 12 FB FB/CP cultures, respectively, MSC(M) expanded both conditions retained immunophenotype. MSC‐EVs identified conditioned medium collected from all STR cultures by transmission electron microscopy, EV protein markers Western blot analysis. no significant differences observed between isolated two feeding approaches. mean sizes 163 5.27 nm 162 4.44 ( p > 0.05) concentrations (2.4 0.35) 11 EVs/mL 0.48) estimated nanoparticle tracking analysis respectively. STR‐based platform optimized herein represents major contribution toward development MSC‐ MSC‐EV‐based products as promising agents Regenerative Medicine settings.

Language: Английский

Citations

14
Lipoprotein apheresis affects the concentration of extracellular vesicles in patients with elevated lipoprotein (a) DOI Creative Commons
Joanna Marlęga-Linert, Aleksandra Gąsecka, Edwin van der Pol

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 2, 2024

Abstract Lipoprotein apheresis (LA) is a therapeutic option for hyperlipoproteinemia(a) (hyper-Lp(a)) and atherosclerotic cardiovascular disease (ASCVD). LA improves blood rheology, reduces oxidative stress parameters endothelial function. The underlying molecular mechanisms of beneficial effects are unknown, but it has been suggested that exhibits multiple activities beyond simply removing lipoproteins. We hypothesized removes not only lipoproteins, also extracellular vesicles (EVs). To test this hypothesis, we performed prospective study in 22 patients undergoing hyper-Lp(a) ASCVD. Different EVs subtypes were measured before directly after LA, 7 days. used calibrated flow cytometry to detect total particle concentration (diameter > ~ 100 nm), lipoproteins 200 nm, RI 1.51), EV < 1.41), concentrations derived from erythrocytes (CD235a+; diameter leukocytes (CD45+; 1.41) platelets (CD61+, PEVs; 1.41). reduced the all investigated Lp(a) was lowered by 64.5% [(58% – 71%); p 0.001]. Plasma nm (CD61 +), (CD45+) (CD235a+) decreased single procedure 42.7% [(12.8–54.7); = 0.005], 42.6% [(29.7–54.1); 0.030] 26.7% [(1.0–62.7); 0.018], respectively, compared baseline. All returned baseline plasma conclude, Lp(a), cell-derived EVs, which may contribute effects.

Language: Английский

Citations

5
Exploring the role of epicardial adipose-tissue-derived extracellular vesicles in cardiovascular diseases DOI Creative Commons
Alessandra Stefania Rizzuto, Guido Gelpi, Andrea Mangini

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(4), P. 109359 - 109359

Published: Feb. 29, 2024

Epicardial adipose tissue (EAT) is a fat depot located between the myocardium and visceral layer of epicardium, which, owing to its location, can influence surrounding tissues act as local transducer systemic inflammation. The mechanisms upon which such depends on are however unclear. Given role EAT undoubtedly has in scheme cardiovascular diseases (CVDs), understanding impact cellular components upmost importance. Extracellular vesicles (EVs) constitute promising candidates fill gap knowledge concerning unexplored through promotes onset progression CVDs. Owing their ability transporting active biomolecules, EAT-derived EVs have been reported be actively involved pathogenesis ischemia/reperfusion injury, coronary atherosclerosis, heart failure, atrial fibrillation. Exploring precise functions exert this context may aid connecting dots

Language: Английский

Citations

5
OxLDL sensitizes platelets for increased formation of extracellular vesicles capable of finetuning macrophage gene expression DOI Creative Commons
Katariina Maaninka, Maarit Neuvonen, Erja Kerkelä

et al.

European Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 102(2), P. 151311 - 151311

Published: March 15, 2023

Platelet extracellular vesicles (PEVs) generated upon platelet activation may play a role in inflammatory pathologies such as atherosclerosis. Oxidized low-density lipoprotein (oxLDL), well-known contributor to atherogenesis, activates platelets and presensitizes them for by other agonists. We studied the effect of oxLDL on secretion, composition, functions PEVs using contemporary EV analytics. Platelets were activated co-stimulation with thrombin (T) collagen (C) ± characterized high-resolution flow cytometry, nanoparticle tracking analysis, proximity extension assay, western blot, electron microscopy. The macrophage differentiation functionality was examined analyzing surface markers, cytokine transcriptome. OxLDL upregulated TC-induced formation CD61+, P-selectin+ phosphatidylserine+ PEVs. Blocking scavenger receptor CD36 significantly suppressed oxLDL+TC-induced PEV formation, HDL caused slight but detectable suppression. protein cargo differed between from stimulated unstimulated platelets. Both oxLDL+TC- enhanced HLA-DR CD86 expression decreased CD11c well secretion several cytokines. Pathways related cell cycle regulation gene expression, immune system signaling overrepresented differentially expressed genes TC -treated vs. control macrophages oxLDL+TC macrophages, respectively. In conclusion, we speculate that contribute proatherogenic processes increasing number provide an adhesive procoagulant surface, contain mediators, subtly finetune expression.

Language: Английский

Citations

11
Extracellular vesicles in heart failure DOI
Alexander Е. Berezin, Alexander A. Berezin

Advances in clinical chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 32

Published: Jan. 1, 2024

Language: Английский

Citations

4
Extracellular vesicles: A new frontier in the theranostics of cardiovascular diseases DOI Creative Commons
Enze Fu, Zongjin Li

iRadiology, Journal Year: 2024, Volume and Issue: 2(3), P. 240 - 259

Published: May 23, 2024

Abstract Extracellular vesicles (EVs) are tiny released by various cells that contain a variety of proteins, lipids, and nucleic acids, which can have wide range effects on other cells. The dynamic composition contents EVs serve as sensitive biomarkers for diagnosing monitoring cardiovascular diseases (CVDs). In addition to their diagnostic potential, therapeutic agents capable precise modulation amelioration CVDs, because innate ability encapsulate deliver bioactive molecules. This growing field reveals the intricate interplay between pathophysiology, showing act messengers intercellular communication CVD regenerative therapy. dual in theranostics, both able decode nuanced molecular signatures CVDs potent vehicles targeted interventions. review delves into evolving landscape EVs, uncovering prospects emphasizing importance shaping future theranostics.

Language: Английский

Citations

4