Emerging role of non-coding RNAs and extracellular vesicles in cardioprotection by remote ischemic conditioning of the heart

(1) Background: Extracellular vesicles (EVs) have been recognized as a cellular communication tool with cardioprotective properties; however, it is unknown whether cardioprotection by remote ischemic conditioning (RIC) involves EVs. (2) Methods: We randomized patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) to additionally receive a protocol of RIC or a sham-intervention. Blood was taken before and immediately, 24 h, four days and one month after PCI. Additionally, we investigated EVs from healthy volunteers undergoing RIC. EVs were characterized by a high-sensitive flow cytometer (Beckman Coulter Cytoflex S, Krefeld, Germany). (3) Results: We analyzed 32 patients (16 RIC, 16 control) and five healthy volunteers. We investigated platelet-, endothelial-, leukocyte-, monocyte- and granulocyte-derived EVs and their pro-thrombotic sub-populations expressing superficial phosphatidylserine (PS+). We did not observe a significant effect of RIC on the numbers of circulating EVs, although granulocyte-derived EVs were significantly higher in the RIC group. In line, RIC had not impact on EVs in healthy volunteers. Additionally, we observed changes of PS+/PEV, EEVs and PS+/CD15+ EVs irrespective of RIC with time following STEMI. 4) Conclusion: We provide further insights into the course of different circulating EVs during the acute and sub-acute phases of STEMI. With respect to the investigated EV populations, RIC seems to have no effect, with only minor differences found for granulocyte EVs.

Download Full-text

The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis

International Journal of Molecular Sciences ◽

10.3390/ijms21228682 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8682 ◽

Cited By ~ 2

Author(s):

Maurizio Muraca ◽

Alfredo Cappariello

Keyword(s):

Bone Metabolism ◽

Extracellular Vesicles ◽

Epigenetic Regulation ◽

Bone Cells ◽

Disease Onset ◽

Powerful Means ◽

Fine Regulation ◽

Non Coding Rnas ◽

Epigenetic Processes

Extracellular vesicles (EVs) are complex phospholipidic structures actively released by cells. EVs are recognized as powerful means of intercellular communication since they contain many signaling molecules (including lipids, proteins, and nucleic acids). In parallel, changes in epigenetic processes can lead to changes in gene function and finally lead to disease onset and progression. Recent breakthroughs have revealed the complex roles of non-coding RNAs (microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)) in epigenetic regulation. Moreover, a substantial body of evidence demonstrates that non-coding RNAs can be shuttled among the cells and tissues via EVs, allowing non-coding RNAs to reach distant cells and exert systemic effects. Resident bone cells, including osteoclasts, osteoblasts, osteocytes, and endothelial cells, are tightly regulated by non-coding RNAs, and many of them can be exported from the cells to neighboring ones through EVs, triggering pathological conditions. For these reasons, researchers have also started to exploit EVs as a theranostic tool to address osteoporosis. In this review, we summarize some recent findings regarding the EVs’ involvement in the fine regulation of non-coding RNAs in the context of bone metabolism and osteoporosis.

Download Full-text

Extracellular Vesicles in Cancer Metabolism: Implications for Cancer Diagnosis and Treatment

Technology in Cancer Research & Treatment ◽

10.1177/15330338211037821 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110378

Author(s):

Qian Zhang ◽

Xiangling Yang ◽

Huanliang Liu

Keyword(s):

Cancer Cells ◽

Extracellular Vesicles ◽

Cancer Diagnosis ◽

Cancer Metabolism ◽

Metabolic Reprogramming ◽

Bioactive Molecules ◽

Diagnosis And Treatment ◽

Existing Problems ◽

Non Coding Rnas

Metabolic reprogramming is one of the most common characteristics of cancer cells. The metabolic alterations of glucose, amino acids and lipids can support the aggressive phenotype of cancer cells. Exosomes, a kind of extracellular vesicles, participate in the intercellular communication through transferring bioactive molecules. Increasing evidence has demonstrated that enzymes, metabolites and non-coding RNAs in exosomes are responsible for the metabolic alteration of cancer cells. In this review, we summarize the past and recent findings of exosomes in altering cancer metabolism and elaborate on the role of the specific enzymes, metabolites and non-coding RNAs transferred by exosomes. Moreover, we give evidence of the role of exosomes in cancer diagnosis and treatment. Finally, we discuss the existing problems in the study and application of exosomes in cancer diagnosis and treatment.

Download Full-text

Antigen-presenting cell-derived extracellular vesicles in accelerating atherosclerosis

Biomedical Research and Therapy ◽

10.15419/bmrat.v8i3.664 ◽

2021 ◽

Vol 8 (3) ◽

pp. 4258-4265

Author(s):

Alexander E Berezin ◽

Alexander A Berezin

Keyword(s):

Extracellular Vesicles ◽

T Regulatory Cells ◽

Bioactive Molecules ◽

Atherosclerotic Plaques ◽

Macrophage Phenotype ◽

Non Coding Rnas ◽

Microvascular Inflammation ◽

Antigen Presenting ◽

Endosomal System

Extracellular vesicles (EVs) are a population of heterogeneous particles that originate from the endosomal system or plasma membrane. Antigen-presenting cells (APCs) produce and release a broad spectrum of EVs involved in the pathogenesis of atherosclerosis. APC-derived EVs contain several bioactive molecules, such as non-coding RNAs, cytokines, chemokines, active proteins, immunomodulatory factors, and growth factors. The review focuses on the role of APC-derived EVs in regulating the transformation of macrophage phenotype, shaping foam cells, driving autophagy and/or inhibiting apoptosis of Th4+ cells, T regulatory cells, endothelial and smooth muscle cells (SMCs), as well as in facilitating oxidative stress in vasculature. APC-derived EVs act as triggers of angiogenesis, neovascularization and inflammation through their participation in microvascular inflammation, angiogenesis, development of atherosclerotic plaques, and modulation of their instability.

Download Full-text

Remote Ischemic Conditioning Improves Post-Ischemic Cardiac Function: The Role of Neuregulin-1

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0037-1598940 ◽

2017 ◽

Vol 65 (S 01) ◽

pp. S1-S110

Author(s):

A. Kiss ◽

P. Pilz ◽

I.F. Gonçalves ◽

M. Inci ◽

F. Nagel ◽

...

Keyword(s):

Cardiac Function ◽

Remote Ischemic Conditioning ◽

Neuregulin 1 ◽

Ischemic Conditioning

Download Full-text

Targeting Inflammation after Myocardial Infarction: A Therapeutic Opportunity for Extracellular Vesicles?

International Journal of Molecular Sciences ◽

10.3390/ijms22157831 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7831

Author(s):

Margarida Viola ◽

Saskia C. A. de Jager ◽

Joost P. G. Sluijter

Keyword(s):

Myocardial Infarction ◽

Immune System ◽

Extracellular Vesicles ◽

Cardiac Inflammation ◽

Stem And Progenitor Cells ◽

Therapeutic Opportunity ◽

Strong Inflammatory Response ◽

Non Coding Rnas ◽

Dead Tissue

After myocardial infarction (MI), a strong inflammatory response takes place in the heart to remove the dead tissue resulting from ischemic injury. A growing body of evidence suggests that timely resolution of this inflammatory process may aid in the prevention of adverse cardiac remodeling and heart failure post-MI. The present challenge is to find a way to stimulate this process without interfering with the reparative role of the immune system. Extracellular vesicles (EVs) are natural membrane particles that are released by cells and carry different macromolecules, including proteins and non-coding RNAs. In recent years, EVs derived from various stem and progenitor cells have been demonstrated to possess regenerative properties. They can provide cardioprotection via several mechanisms of action, including immunomodulation. In this review, we summarize the role of the innate immune system in post-MI healing. We then discuss the mechanisms by which EVs modulate cardiac inflammation in preclinical models of myocardial injury through regulation of monocyte influx and macrophage function. Finally, we provide suggestions for further optimization of EV-based therapy to improve its potential for the treatment of MI.

Download Full-text

Immune Modulation as a Key Mechanism for the Protective Effects of Remote Ischemic Conditioning After Stroke

Frontiers in Neurology ◽

10.3389/fneur.2021.746486 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sima Abbasi-Habashi ◽

Glen C. Jickling ◽

Ian R. Winship

Keyword(s):

Immune Modulation ◽

Ischemia Reperfusion ◽

Treatment Strategies ◽

Protective Effects ◽

Humoral Factors ◽

Remote Ischemic Conditioning ◽

Ischemic Conditioning ◽

Mediators Of Inflammation ◽

The Brain

Remote ischemic conditioning (RIC), which involves a series of short cycles of ischemia in an organ remote to the brain (typically the limbs), has been shown to protect the ischemic penumbra after stroke and reduce ischemia/reperfusion (IR) injury. Although the exact mechanism by which this protective signal is transferred from the remote site to the brain remains unclear, preclinical studies suggest that the mechanisms of RIC involve a combination of circulating humoral factors and neuronal signals. An improved understanding of these mechanisms will facilitate translation to more effective treatment strategies in clinical settings. In this review, we will discuss potential protective mechanisms in the brain and cerebral vasculature associated with RIC. We will discuss a putative role of the immune system and circulating mediators of inflammation in these protective processes, including the expression of pro-and anti-inflammatory genes in peripheral immune cells that may influence the outcome. We will also review the potential role of extracellular vesicles (EVs), biological vectors capable of delivering cell-specific cargo such as proteins and miRNAs to cells, in modulating the protective effects of RIC in the brain and vasculature.

Download Full-text