Circulating blood cells and extracellular vesicles in acute cardioprotection

Abstract

During an ST-elevation myocardial infarction (STEMI), the myocardium undergoes a prolonged period of ischaemia. Reperfusion therapy is essential to minimize cardiac injury but can paradoxically cause further damage. Experimental procedures to limit ischaemia and reperfusion (IR) injury have tended to focus on the cardiomyocytes since they are crucial for cardiac function. However, there is increasing evidence that non-cardiomyocyte resident cells in the heart (as discussed in a separate review in this Spotlight series) as well as circulating cells and factors play important roles in this pathology. For example, erythrocytes, in addition to their main oxygen-ferrying role, can protect the heart from IR injury via the export of nitric oxide bioactivity. Platelets are well-known to be involved in haemostasis and thrombosis, but beyond these roles, they secrete numerous factors including sphingosine-1 phosphate (S1P), platelet activating factor, and cytokines that can all strongly influence the development of IR injury. This is particularly relevant given that most STEMI patients receive at least one type of platelet inhibitor. Moreover, there are large numbers of circulating vesicles in the blood, including microvesicles and exosomes, which can exert both beneficial and detrimental effects on IR injury. Some of these effects are mediated by the transfer of microRNA (miRNA) to the heart. Synthetic miRNA molecules may offer an alternative approach to limiting the response to IR injury. We discuss these and other circulating factors, focussing on potential therapeutic targets relevant to IR injury. Given the prevalence of comorbidities such as diabetes in the target patient population, their influence will also be discussed. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.

Dilated cardiomyopathy

“…Promising new tools include mesenchymal stem cells, purified platelet exosome products, fat-derived extracellular vesicles and others. Extracellular vesicles and the more-purified form termed exosomes derived from cells such as adipocytes or platelets of healthy individuals are important in cell-to-cell communication and have been found to contain many regulatory factors such as proteins, RNAs and lipids that inhibit pro-inflammatory and profibrotic pathology 216 . Although many of these therapies have yet to be applied to patients with DCM in the clinical setting, they hold the promise of a therapy that could prevent or reverse remodelling and promote cardiac regeneration 217,218 .…”

Sex is no determinant of cardioprotection by ischemic preconditioning in rats, but ischemic/reperfused tissue mass is for remote ischemic preconditioning

“…The translation of cardioprotection by ischemic conditioning to clinical practice has been largely disappointing so far (Heusch 2017;Davidson et al 2019a). Such failure of translation is, apart from details of the underlying signal transduction of cardioprotection and strategies of its recruitment (Heusch 2015;Andreadou et al 2019;Davidson et al 2019b;Hausenloy et al 2019aHausenloy et al ,2019bZuurbier et al 2019), due to the lack of an optimal algorithm of the conditioning stimulus (duration and number of ischemia/reperfusion cycles, as well as its temporal distance to the index ischemia). Clinical Phase II studies to identify an optimal conditioning algorithm do not exist at all.…”

Depletion of erythropoietic miR-486-5p and miR-451a improves detectability of rare microRNAs in peripheral blood-derived small RNA sequencing libraries

“…and cell-derived components (platelets, exosomes, etc.) suspended in a medium known as plasma (23). Besides blood-cell expressed miR-NAs, blood also contains circulating miRNAs that are detected in serum, plasma or exosomes (24).…”