Cardioprotection by remote ischemic preconditioning of the rat heart is mediated by extracellular vesicles

Giricz, Zoltán; Varga, Zoltán V.; Baranyai, Tamás; Sipos, Péter; Pálóczi, Krisztina; Kittel, Ágnes; Buzás, Edit I.; Ferdinándy, Péter

doi:10.1016/j.yjmcc.2014.01.004

Cited by 236 publications

(201 citation statements)

References 15 publications

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“…Recently, involvement of the SDF-1a/CXCR4 axis has been shown . Also, cardioprotection by remote ischemic preconditioning of the rat heart was recently shown to be mediated by extracellular vesicles released by brief periods of ischemia and acting as potential carriers of cardioprotective substances (Giricz et al, 2014). A comprehensive discussion of the potential mechanisms underlying remote ischemic conditioning is beyond the scope of this review, and the reader is referred to comprehensive reviews on the subject Vinten-Johansen and Shi, 2013).…”

Section: Cardioprotection Through Remote Conditioningmentioning

confidence: 99%

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

Ferdinándy¹,

Hausenloy²,

Heusch³

et al. 2014

Pharmacol Rev

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506

491

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Section: Cardioprotection Through Remote Conditioningmentioning

confidence: 99%

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

Ferdinándy¹,

Hausenloy²,

Heusch³

et al. 2014

Pharmacol Rev

Self Cite

506

491

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“…or myocyte hypertrophic signals, or even by delivery from distant sites, as found in remote preconditioning 144,145 . In addition to exosomes, tunnelling nanotubes -long, intercellular connections of 50-700 nm in diameter prov iding membrane continuity between connected cells -have emerged as an alternative means of transfer of microRNAs and even organelles 146,147 .…”

Section: Nature Reviews | Cardiologymentioning

confidence: 99%

Proteostasis in cardiac health and disease

Henning

Brundel²

2017

Nat Rev Cardiol

132

111

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The worldwide increase in life expectancy gives rise to an increasing prevalence of cardiac diseases, which remain the leading cause of disability and death in the developed world [1][2][3] . Currently, the mechanisms under lying how ageing contributes to the initiation or acceler ation of cardiac diseases are essentially unresolved. Prevailing theories of ageing centre on gradual derail ment of cellular protein homeostasis -proteostasis -either by design (genetically) or by 'wear and tear' (environmentally) 3 . Central to the role of proteostasis derailment as a major factor in ageing is the observation that protein function declines over time.Proteins are the most versatile and complex macro molecules and are involved in the proper functioning of every biological process 4 . After synthesis as a poly peptide chain from the genetic code, proper function of a protein relies heavily on its correct folding into a 3D native state and on various post translational modifi cations, mostly involving the addition of chem ical groups (including phosphate, acetate, and carbo hydrate). Protein maturation, transport, and ultimately breakdown is monitored and supported by various classes of proteins, collectively called 'protein quality control' (PQC) [3][4][5] . Balanced proteostasis, therefore, depends on proper PQC and is crucial for cellular and organismal health 6 . The intricate network making up the PQC involves numerous proteins, of which the main players are the chaperones and their regula tors 4,7-9 (assisting in folding and refolding of proteins) and the pathways that clear irreversibly misfolded and aggregation prone proteins (the ubiquitin-proteasome system [UPS] and autophagy systems) 9-11 . With ageing, the gradual accumulation of misfolded or damaged pro teins, together with concomitant failure of PQC, results in proteotoxic stress and compromised defence against reactive oxygen species (ROS) 10 , a process that is likely to be accelerated in various age related diseases includ ing neurodegenerative diseases 12,13 , type 2 diabetes mel litus 14 , cancer 15 , and cardiac diseases [16][17][18][19][20] . In addition to the accumulation of misfolded proteins, ageing is accompanied by an imbalance in the proteome, as indi cated by lowered expression of chaperone, proteaso mal, ribosomal, and mitochondrial proteins, whereas proteins related to oxidative stress are upregulated 21,22 . Although mild impairment of proteostasis extends lifespan in Caenorhabditis elegans, referred to as hormesis, sustained impairment is accompanied by loss of PQC to neutralize this effect 3,5 . Importantly, evidence indicates that the amount of soluble, aggregate prone protein oligomers, rather than the abundance of pro tein aggregates, correlates with disease severity 23,24 . Therefore, protein aggregates, which contain both misfolded proteins and elevated levels of chaper ones, constitute an adequate PQC response, aimed at sequestering potentially harmful protein oligomers, rather than embodying the ultimate cellular threat 25 . This ...

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“…The main benefit of mesenchymal stem cells may be derived from the bioactive encapsulated molecules they secrete in the form of EVs 7. EVs have been shown to improve blood flow and cardiac function in rodent or porcine models of acute or chronic myocardial infarction 8, 9, 10, 11. We did not observe myocardial infarction in our ameroid model of chronic myocardial ischemia.…”

Section: Discussionmentioning

confidence: 53%

“…The release of extracellular vesicles from mesenchymal cells is thought to induce angiogenesis, promote proliferation and differentiation of host cells, inhibit apoptosis, modulate immune function, and recruit endogenous stem cells 7. Extracellular vesicles have been shown to be cardioprotective in small and large animal models of acute and chronic myocardial infarct 8, 9, 10, 11. Although acute and chronic myocardial diseases often coincide, myocardial infarct and chronic myocardial ischemia are distinct disease processes 12.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia

Potz

Scrimgeour

Pavlov

et al. 2018

JAHA

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BackgroundMesenchymal stem cell–derived extracellular vesicles (EVs) are believed to be cardioprotective in myocardial infarct. The objective of this study was to examine the effects of human mesenchymal cell–derived EV injection on cardiac function, myocardial blood flow, and vessel density in the setting of chronic myocardial ischemia.Methods and ResultsTwenty‐three Yorkshire swine underwent placement of an ameroid constrictor on their left circumflex artery. Two weeks later, the animals were split into 2 groups: the control group (CON; n=7) and the EV myocardial injection group (MVM; n=10). The MVM group underwent myocardial injection of 50 μg of EVs in 2 mL 0.9% saline into the ischemic myocardium. Five weeks later, the pigs underwent a harvest procedure, and the left ventricular myocardium was analyzed. Absolute blood flow and the ischemic/nonischemic myocardial perfusion ratio were increased in the ischemic myocardium in the MVM group compared with the CON group. Pigs in the MVM group had increased capillary and arteriolar density in the ischemic myocardial tissue compared with CON pigs. There was an increase in expression of the phospho–mitogen‐activated protein kinase/mitogen‐activated protein kinase ratio, the phospho–endothelial nitric oxide synthase/endothelial nitric oxide synthase ratio, and total protein kinase B in the MVM group compared with CON. There was an increase in cardiac output and stroke volume in the MVM group compared with CON.ConclusionsIn the setting of chronic myocardial ischemia, myocardial injection of human mesenchymal cell–derived EVs increases blood flow to ischemic myocardial tissue by induction of capillary and arteriolar growth via activation of the protein kinase B/endothelial nitric oxide synthase and mitogen‐activated protein kinase signaling pathways resulting in increased cardiac output and stroke volume.

show abstract

Cardioprotection by remote ischemic preconditioning of the rat heart is mediated by extracellular vesicles

Cited by 236 publications

References 15 publications

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

Proteostasis in cardiac health and disease

Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia

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