Differential clusterization of soluble and extracellular vesicle-associated cytokines in myocardial infarction

Lebedeva, A.; Fitzgerald, Wendy; Molodtsov, Ivan; Shpektor, A.; Vasilieva, Elena; Margolis, Leonid

doi:10.1038/s41598-020-78004-y

Cited by 10 publications

(5 citation statements)

References 80 publications

(155 reference statements)

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“…Previous evidence, similar to our results, has described an increase in circulating IP-10 in patients with acute myocardial infarction associated with the size of the infarct [32]; other investigations have not found a change in TNF-α between healthy subjects and patients, similar to our results [20]. Consistent with our results, another study demonstrated high concentration levels of IL-1β, IL-6 and IL-12p70 in patients with STEMI [33] and showed that these were associated with a lower improvement response in patients with advanced heart failure [34]. These results indicate a highly inflammatory environment in patients with STEMI, which could favor postinfarction pathogenesis.…”

Section: Discussionsupporting

confidence: 93%

Human Bone Marrow Mesenchymal Stem Cells Promote the M2 Phenotype in Macrophages Derived from STEMI Patients

Cortés-Morales,

Vázquez-González,

Montesinos

et al. 2023

IJMS

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Acute ST-elevation myocardial infarction (STEMI) leads to myocardial injury or necrosis, and M1 macrophages play an important role in the inflammatory response. Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are capable of modulating macrophage plasticity, principally due to their immunoregulatory capacity. In the present study, we analyzed the capacity of MSCs to modulate macrophages derived from monocytes from patients with STEMI. We analyzed the circulating levels of cytokines associated with M1 and M2 macrophages in patients with STEMI, and the levels of cytokines associated with M1 macrophages were significantly higher in patients with STEMI than in controls. BM-MSCs facilitate the generation of M1 and M2 macrophages. M1 macrophages cocultured with MSCs did not have decreased M1 marker expression, but these macrophages had an increased expression of markers of the M2 macrophage phenotype (CD14, CD163 and CD206) and IL-10 and IL-1Ra signaling-induced regulatory T cells (Tregs). M2 macrophages from patients with STEMI had an increased expression of M2 phenotypic markers in coculture with BM-MSCs, as well as an increased secretion of anti-inflammatory cytokines and an increased generation of Tregs. The findings in this study indicate that BM-MSCs have the ability to modulate the M1 macrophage response, which could improve cardiac tissue damage in patients with STEMI.

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Section: Discussionsupporting

confidence: 93%

Human Bone Marrow Mesenchymal Stem Cells Promote the M2 Phenotype in Macrophages Derived from STEMI Patients

Cortés-Morales,

Vázquez-González,

Montesinos

et al. 2023

IJMS

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“…Moreover, EVs have been known to carry or present cytokines on their surface, including TNFα, IL1β, and IL6 [ 35 ]. This aligns with findings in clinical settings, such as in patients with myocardial infarction, where EV-associated cytokines have shown dysregulation [ 36 ].…”

Section: Discussionsupporting

confidence: 88%

Induction of Neuroinflammation and Brain Oxidative Stress by Brain-Derived Extracellular Vesicles from Hypertensive Rats

Chen,

Yan,

Gingerich

et al. 2024

Antioxidants

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Neuroinflammation and brain oxidative stress are recognized as significant contributors to hypertension including salt sensitive hypertension. Extracellular vesicles (EVs) play an essential role in intercellular communication in various situations, including physiological and pathological ones. Based on this evidence, we hypothesized that EVs derived from the brains of hypertensive rats with salt sensitivity could trigger neuroinflammation and oxidative stress during hypertension development. To test this hypothesis, we compared the impact of EVs isolated from the brains of hypertensive Dahl Salt-Sensitive rats (DSS) and normotensive Sprague Dawley (SD) rats on inflammatory factors and mitochondrial reactive oxygen species (mtROS) production in primary neuronal cultures and brain cardiovascular relevant regions, including the hypothalamic paraventricular nucleus (PVN) and lamina terminalis (LT). We found that brain-derived DSS-EVs significantly increased the mRNA levels of proinflammatory cytokines (PICs) and chemokines, including TNFα, IL1β, CCL2, CCL5, and CCL12, as well as the transcriptional factor NF-κB in neuronal cultures. DSS-EVs also induced oxidative stress in neuronal cultures, as evidenced by elevated NADPH oxidase subunit CYBA coding gene mRNA levels and persistent mtROS elevation. When DSS-EVs were injected into the brains of normal SD rats, the mRNA levels of PICs, chemokines, and the chronic neuronal activity marker FOSL1 were significantly increased in the PVN and LT. Furthermore, DSS-EVs caused mtROS elevation in brain PVN and LT, particularly in neurons. Our study reveals a novel role for brain-derived EVs from hypertensive rats in triggering neuroinflammation, upregulating chemokine expression, and inducing excessive ROS production. These findings provide insight into the complex interactions between EVs and hypertension-associated processes, offering potential therapeutic targets for hypertension-linked neurological complications.

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“…In agreement, transcriptome data was correlated with an upregulation of regulatory genes involved in inflammatory responses and ECM following post-MI healing (Li et al, 2019) and isoproterenol-induced hypertrophy (Lau et al, 2018). A significant dysregulation of long non-coding RNA was found in cardiac fibroblasts upon pressure overload (Piccoli et al, 2017), while distinctive patterns of circulating soluble cytokines (Lebedeva et al, 2020), EV-enclosed proteins and miRNA (Otero-Ortega et al, 2021) were also identified, corroborating the importance of long-distance intra-cardiac and systemic communication in remodeling of the heart.…”

Section: Intercellular Communication Changes Associated With Myocardial Infarction Hypertrophy and Heart Failuresupporting

confidence: 65%

Connecting different heart diseases through intercellular communication

Martins‐Marques

2021

Biology Open

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Well-orchestrated intercellular communication networks are pivotal to maintaining cardiac homeostasis and to ensuring adaptative responses and repair after injury. Intracardiac communication is sustained by cell–cell crosstalk, directly via gap junctions (GJ) and tunneling nanotubes (TNT), indirectly through the exchange of soluble factors and extracellular vesicles (EV), and by cell–extracellular matrix (ECM) interactions. GJ-mediated communication between cardiomyocytes and with other cardiac cell types enables electrical impulse propagation, required to sustain synchronized heart beating. In addition, TNT-mediated organelle transfer has been associated with cardioprotection, whilst communication via EV plays diverse pathophysiological roles, being implicated in angiogenesis, inflammation and fibrosis. Connecting various cell populations, the ECM plays important functions not only in maintaining the heart structure, but also acting as a signal transducer for intercellular crosstalk. Although with distinct etiologies and clinical manifestations, intercellular communication derailment has been implicated in several cardiac disorders, including myocardial infarction and hypertrophy, highlighting the importance of a comprehensive and integrated view of complex cell communication networks. In this review, I intend to provide a critical perspective about the main mechanisms contributing to regulate cellular crosstalk in the heart, which may be considered in the development of future therapeutic strategies, using cell-based therapies as a paradigmatic example. This Review has an associated Future Leader to Watch interview with the author.

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Differential clusterization of soluble and extracellular vesicle-associated cytokines in myocardial infarction

Cited by 10 publications

References 80 publications

Human Bone Marrow Mesenchymal Stem Cells Promote the M2 Phenotype in Macrophages Derived from STEMI Patients

Human Bone Marrow Mesenchymal Stem Cells Promote the M2 Phenotype in Macrophages Derived from STEMI Patients

Induction of Neuroinflammation and Brain Oxidative Stress by Brain-Derived Extracellular Vesicles from Hypertensive Rats

Connecting different heart diseases through intercellular communication

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