Exosomes and cardioprotection - A critical analysis

Exosomes are nano-sized vesicles released by numerous cell types that appear to have diverse beneficial effects on the injured heart. Studies using exosomes from stem cells or from the blood have indicated that they are able to protect the heart both in models of acute ischaemia and reperfusion, and during chronic ischaemia. In addition to decreasing initial infarct size, they are able to stimulate angiogenesis, reduce fibrosis and remodelling, alter immune cell function and improve long-term cardiac contractile function. However, since the technology and techniques used for the study of exosomes is relatively immature and continually evolving, there remain many important caveats to the interpretation of studies. This review presents a critical analysis of the field of exosomes and cardioprotection. We analyse the effects of exosomes from all types of stem cells investigated to date, summarize the major effects observed and their potential mechanism, and offer our perspective on the major outstanding issues

Investigation of a swirling flow nozzle for a fluidised bed gas distributor

This paper relates to a multi-orifice distributor for a gas-fluidised bed, using many upward-facing nozzles, equally spaced in a horizontal plate. Each orifice contained a removable helical coil, which made the gas swirl as it entered the bed. For a single orifice in such a distributor, ultra-fast magnetic resonance imaging (MRI) and pressure measurements were applied to study: (i) the formation of jets and bubbles and (ii) the orifice pressure drop. Results from MRI show that the swirling flow induced by the helix significantly improves the fluidisation quality compared to a plain nozzle without spiral. The helix gives rise to secondary flow which increases pressure drop across the nozzle, the measured values of which are predicted satisfactorily by using a friction factor correlation for helical coils.The authors thank Dr Stephen Sutcliffe and Mo Dadvar of Huntsman for providing both financial and technical assistance for this project, and Suttons Seeds for the kind donation of poppy seeds used for MRI. S.M. Aworinde is grateful to the Cambridge Commonwealth Trust (CCT) for scholarship award to study at Cambridge

Exosomes and Cardiovascular Protection

Most, if not all, cells of the cardiovascular system secrete small, lipid bilayer vesicles called exosomes. Despite technical challenges in their purification and analysis, exosomes from various sources have been shown to be powerfully cardioprotective. Indeed, it is possible that much of the so-called "paracrine" benefit in cardiovascular function obtained by stem cell therapy can be replicated by the injection of exosomes produced by stem cells. However, exosomes purified from plasma appear to be just as capable of activating cardioprotective pathways. We discuss the potential roles of endogenous exosomes in the cardiovascular system, how this is perturbed in cardiovascular disease, and evaluate their potential as therapeutic agents to protect the heart

Fantastic beasts and how to find them—Molecular identification of the mitochondrial ATP-sensitive potassium channel

Despite reported sightings over many years, certain mitochondrial-specific channels have proven to be elusive beasts, evading molecular identification. However, combining modern genetics with a wave of their ion-sensing wand, researchers have managed to capture first the mitochondrial calcium uniporter, and now that semi-mythological beast, the mitochondrial ATP-sensitive potassium (mitoKATP) channel

Does remote ischaemic conditioning reduce inflammation? A focus on innate immunity and cytokine response

The benefits of remote ischaemic conditioning (RIC) have been difficult to translate to humans, when considering traditional outcome measures, such as mortality and heart failure. This paper reviews the recent literature of the anti-inflammatory effects of RIC, with a particular focus on the innate immune response and cytokine inhibition. Given the current COVID-19 pandemic, the inflammatory hypothesis of cardiac protection is an attractive target on which to re-purpose such novel therapies. A PubMed/MEDLINE™ search was performed on July 13th 2020, for the key terms RIC, cytokines, the innate immune system and inflammation. Data suggest that RIC attenuates inflammation in animals by immune conditioning, cytokine inhibition, cell survival and the release of anti-inflammatory exosomes. It is proposed that RIC inhibits cytokine release via a reduction in nuclear factor kappa beta (NF-κB)-mediated NLRP3 inflammasome production. In vivo, RIC attenuates pro-inflammatory cytokine release in myocardial/cerebral infarction and LPS models of endotoxaemia. In the latter group, cytokine inhibition is associated with a profound survival benefit. Further clinical trials should establish whether the benefits of RIC in inflammation can be observed in humans. Moreover, we must consider whether uncomplicated MI and elective surgery are the most suitable clinical conditions in which to test this hypothesis

The Role of Extracellular DNA and Histones in Ischaemia-Reperfusion Injury of the Myocardium

Despite an increase in the rates of survival in patients suffering myocardial infarction, as yet there is no therapy specifically targeting ischaemia and reperfusion injury of the myocardium. With a greater understanding of immune activation during infarction, more potential treatment targets are now being identified. The innate immune system is believed to play an important role in the myocardium after ischaemia-driven cardiomyocyte death. The release of intracellular contents including DNA into the extracellular space during necrosis and cell rupture is now believed to create a pro-inflammatory milieu which propagates the inflammatory process. DNA and DNA fragments have been shown to activate the innate immune system by acting as Danger-Associated Molecular Patterns (DAMPs), which act as ligands on toll-like receptors (TLRs). Stimulation of TLRs, in turn, can activate intracellular cell death pathways such as pyroptosis. Here, we review the role of DNA fragments during ischaemia and reperfusion, and assess their potential as a target in the quest to preserve cardiomyocyte viability following myocardial infarction