Abstract：
:Mesenchymal stromal cells (MSCs) exhibit antiapoptotic and proangiogenic functions in models of myocardial infarction which may be mediated by secreted small extracellular vesicles (sEVs). However, MSCs have frequently been harvested from aged or diseased patients, while the isolated sEVs often contain high levels of impurities. Here, we studied the cardioprotective and proangiogenic activities of size-exclusion chromatography-purified sEVs secreted from human foetal amniotic fluid stem cells (SS-hAFSCs), possessing superior functional potential to that of adult MSCs. We demonstrated for the first time that highly pure (up to 1.7 × 1010 particles/µg protein) and thoroughly characterised SS-hAFSC sEVs protect rat hearts from ischaemia-reperfusion injury in vivo when administered intravenously prior to reperfusion (38 ± 9% infarct size reduction, p < 0.05). SS-hAFSC sEVs did not protect isolated primary cardiomyocytes in models of simulated ischaemia-reperfusion injury in vitro, indicative of indirect cardioprotective effects. SS-hAFSC sEVs were not proangiogenic in vitro, although they markedly stimulated endothelial cell migration. Additionally, sEVs were entirely responsible for the promigratory effects of the medium conditioned by SS-hAFSC. Mechanistically, sEV-induced chemotaxis involved phosphatidylinositol 3-kinase (PI3K) signalling, as its pharmacological inhibition in treated endothelial cells reduced migration by 54 ± 7% (p < 0.001). Together, these data indicate that SS-hAFSC sEVs have multifactorial beneficial effects in a myocardial infarction setting.
journal_name
Basic Res Cardioljournal_title
Basic research in cardiologyauthors
Takov K,He Z,Johnston HE,Timms JF,Guillot PV,Yellon DM,Davidson SMdoi
10.1007/s00395-020-0785-3subject
Has Abstractpub_date
2020-03-07 00:00:00pages
26issue
3eissn
0300-8428issn
1435-1803pii
10.1007/s00395-020-0785-3journal_volume
115pub_type
杂志文章abstract：:Sprouty1 (Spry1) is a negative modulator of receptor tyrosine kinase signaling, but its role in cardiomyocyte survival has not been elucidated. The aim of this study was to investigate the potential role of cardiomyocyte Spry1 in cardiac ischemia-reperfusion (I/R) injury. Infarct areas of mouse hearts showed an increa...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-018-0713-y
更新日期：2019-01-11 00:00:00
abstract：:The purpose of this study was to determine the effects of bradykinin (BK), substance P (SP) and histamine on plasma exudation in the skin of conscious dogs with and without pacing-induced heart failure. We also determined the role tissue angiotensin I-converting enzyme (ACE) and neutral endopeptidase (NEP) play in mod...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF00788284
更新日期：1994-09-01 00:00:00
abstract：:Receptor for advanced glycation end products (RAGE) and connective tissue growth factor (CTGF) play a key role in diabetic myocardial fibrosis, and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation has been reported to reduce RAGE and CTGF expression. This study investigated the effects of the P...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-009-0071-x
更新日期：2010-05-01 00:00:00
abstract：:Using isolated canine small (right coronary branch, left coronary branch; o. d. 0.4-0.8 mm) and large (left coronary, circumflex; o. d. 1-2 mm) coronary arteries, the beta-adrenergic antagonist dl-propranolol (5 X 10(-7) to 5 X 10(-5) m/l) was found to produce concentration-dependent contractions. Interestingly, most ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01908132
更新日期：1982-01-01 00:00:00
abstract：:Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects of CBS on the ventricular electrophysiological properties in canines with chronic heart failure (CHF). Thirty-eight beagles were randomized into contr...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-019-0750-1
更新日期：2019-09-09 00:00:00
abstract：:In the isometrically contracting rat trabecular muscle strip preparation, contracture tension was induced either by 10 min of hypoxia (low contracture tension) or by 30 min of joint oxygen and glucose withdrawal (severe contracture tension) at optimum length. Using stepwise 0.1 mm releases, length-tension relationship...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01908059
更新日期：1981-11-01 00:00:00
abstract：:Although it has long been recognized that thyroid hormone is an effective positive inotrope, its efficacy in supporting hemodynamics in the acute setting of ischaemia and reperfusion (R) without worsening reperfusion injury remains largely unknown. Thus, we investigated the effects of triiodothyronine (T3) on reperfus...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-008-0758-4
更新日期：2009-01-01 00:00:00
abstract：:The influence of cardiac cholinergic activation was studied in rats and cats on the induction and maintenance of ventricular fibrillation (VF). Acetylcholine (ACH 2-25 micrograms/kg), in doses which did not cause bradycardia or hypotension, induced appearance of spontaneous VF (duration 2-60 sec.) in 9/20 rats which h...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01908386
更新日期：1984-11-01 00:00:00
abstract：:Hemodynamics and myocardial contractility were evaluated in five unanesthetized calves during acute hypocapnic and isocapnic hypoxia and during acute hypocapnic hypoxia with beta-adrenergic blockade. Both hypocapnic and isocapnic hypoxia, with mean PaO2 levels of 33.1 and 39.1 mm Hg respectively, produced a decline in...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01909762
更新日期：1976-09-01 00:00:00
abstract：:The clinical use of positive inotropic agents has been associated with increased mortality, with proarrhythmia speculated to be a contributing factor. This study compares the arrhythmogenic potentials of six positive inotropic agents representing different mechanistic classes: the beta-adrenergic agonist dobutamine, t...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s003950050181
更新日期：2000-06-01 00:00:00
abstract：:Implicit in attempts to characterize and purify biologically active factors is the premise that the bioassay system employed will show a progressive increase in the response as the concentration of the responsible factor increases. We employed the hamster cheek pouch to assay the neovascularization potential of growth...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01907406
更新日期：1986-05-01 00:00:00
abstract：:Age-related changes in the myocardial energy metabolism were studied in spontaneously hypertensive (SHR) rats of 5-15 weeks of age. Systolic blood pressure increased rapidly during 5 to 10 weeks of age (developing phase) and attained a plateau level at 10 to 15 weeks (sustained phase). Even during the developing phase...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF02005337
更新日期：1982-07-01 00:00:00
abstract：:The aim of this study was to investigate the mechanism of beta-adrenergic preconditioning (BPC). The roles of adenosine and its receptor subtypes, the generation of oxygen free radicals (ROS) and activation of the K(ATP) channels as well as the phosphoinositide-3-kinase (PI(3)K)/PKB/Akt and extracellular signal-regula...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-012-0281-5
更新日期：2012-09-01 00:00:00
abstract：:Increasing the frequency of steady state stimulation increases the rate of mechanical restitution in hypothermic (27 degrees C) guinea pig papillary muscles. In this paper we have investigated the influences of the calcium antagonist nifedipine and of reduced extracellular calcium concentration on this phenomenon. We ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF00798259
更新日期：1993-03-01 00:00:00
abstract：:Experiments were performed to determine the relative contributions of direct Ca(2+)-entry through the L-type Ca(2+)-current and of Ca(2+)-release from the sarcoplasmic reticulum (s.r.) to the intracellular [Ca2+]i-transient in isolated human atrial and ventricular myocytes from patients with severe heart failure and f...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF00794074
更新日期：1997-01-01 00:00:00
abstract：:The characterization of various ion transport systems has led to a better understanding of the effects, which seem to take part in the impairment of ischemic and reperfused cardiac tissue. This review discusses the role of the Na+/H+ exchange system in the pathophysiology of ischemia and reperfusion and the beneficial...
journal_title：Basic research in cardiology
pub_type： 杂志文章,评审
doi：10.1007/BF00795411
更新日期：1993-09-01 00:00:00
abstract：:K201 has previously been shown to reduce diastolic contractions in vivo during β-adrenergic stimulation and elevated extracellular calcium concentration ([Ca(2+)](o)). The present study characterised the effect of K201 on electrically stimulated and spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca(2+) rel...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-011-0218-4
更新日期：2011-11-01 00:00:00
abstract：:It has been investigated whether calcium- and verapamil-dependent sensitivities of carotis baroreceptors also exist in man. To answer this question, we pre- and postoperatively measured changes in heart rate during carotid sinus stimulation before and after intravenous administration of 5 mg verapamil in 23 patients w...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF00795058
更新日期：1992-09-01 00:00:00
abstract：:The effect of 0.1 mg/kg Verapamil on the extent of the ischemic area following ligation of a branch of the left descending coronary artery was studied in anesthetized open chest dogs. The sum of the ST-segment elevation during the entire period of occlusion in the epicardial ECG was 15 mV in control infarction compare...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01905620
更新日期：1975-03-01 00:00:00
abstract：:The influence of perfusion pressure (5-8 kPa) on coronary flow and myocardial Ca2+-washout during Ca2+-free perfusion, and on the occurrence of calcium paradox after subsequent Ca2+-reperfusion, was studied in isolated, stimulated, rat heart ventricles. During the Ca2+-free perfusion period (3 min) the following chang...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01907580
更新日期：1980-03-01 00:00:00
abstract：:In the chronically volume-overloaded canine heart due to AV-block evaluations of cardiac function were performed during the development of hypertrophy and at stable hypertrophy. In an early stage (1 and 2 weeks of AV-block) when no or only a slight increase of cardiac muscle occurred, contractility measured from dP/dt...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01906357
更新日期：1977-03-01 00:00:00
abstract：:The isolated working rabbit heart preparation was used to study whether the "contractile machinery" remains unchanged in globally stunned myocardium. The function of the heart has been measured in nonischemic and postischemic conditions. The effect of isoprenaline or calcium chloride administration in both conditions ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF02190601
更新日期：1991-05-01 00:00:00
abstract：:Successive ischemic episodes are commonly seen in clinical and experimental cardiology. Although prolonged abnormalities of the canine myocardium have been described following a single ischemic episode, it is not known whether myocardial injury is cumulative following multiple ischemic episodes. Dogs were subjected to...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01908148
更新日期：1984-07-01 00:00:00
abstract：:Protection from postconditioning has been documented in in situ animal models and it has been proposed that it is targeting circulating leukocytes. We therefore tested whether postconditioning can protect leukocyte-free, buffer-perfused rabbit hearts. Infarct size was measured with triphenyltetrazolium staining. In co...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-004-0498-4
更新日期：2005-01-01 00:00:00
abstract：:Alterations in myocardial membrane phospholipids may play an important role in the pathogenesis of ischaemic myocardial cell injury. Studies in canine myocardium, perfused rat heart, and cultured myocardial cells have demonstrated that the accumulation of free arachidonic acid correlates with the development of irreve...
journal_title：Basic research in cardiology
pub_type： 杂志文章,评审
doi：10.1007/978-3-662-08390-1_15
更新日期：1987-01-01 00:00:00
abstract：:There is no doubt that major advances have been made in cardiac electrophysiology using single heart cells. Accurate analysis of rapid inward sodium current and the second inward current carried by calcium has resulted in a major re-examination of the steps involved in excitation-contraction coupling in the heart. Fut...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/978-3-662-11041-6_17
更新日期：1985-01-01 00:00:00
abstract：:Ischaemic preconditioning is one of the most potent experimental modalities known to decrease infarct size after ischaemia and reperfusion. Much interest has been stimulated by the phenomenon of remote ischaemic conditioning (RIC), in which the preconditioning stimulus is applied to a limb remote from the heart to sti...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s00395-013-0377-6
更新日期：2013-09-01 00:00:00
abstract：:Endothelin-1 elicited a concentration-dependent positive inotropic effect on the isolated rabbit, guinea pig, and rat, but not on the dog ventricular myocardium. The duration of isometric contractions was prolonged by endothelin-1 in a concentration-dependent manner, mainly by prolongation of relaxation time. Phorbol ...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:The genetic defect in the cardiomyopathic (CM) hamster is a mutation in the glycoprotein-sarcoglycan (a component of the dystrophin-glycoprotein complex). Apoptosis has been identified in skeletal muscle of dystrophin-deficient mice, and therefore the role of myocardial apoptosis in relation to oncosis in causing myoc...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/s395-002-8389-4
更新日期：2002-01-01 00:00:00
abstract：:The effects of 3 hours of ischemia and 1 hour of reperfusion on biochemical, physiological and ultrastructural parameters were studied in 12 dogs. In the ischemic subendocardium without reperfusion, mitochondrial losses of adenine (ATP + ADP + AMP) and pyridine (NAD + NADH) nucleotides far exceeded those observed in w...
journal_title：Basic research in cardiology
pub_type： 杂志文章
doi：10.1007/BF01908307
更新日期：1984-03-01 00:00:00
