Mobilization of endothelial progenitor cells in acute cardiovascular events in the PROCELL study: Time-course after acute myocardial infarction and stroke

Regueiro, Ander; Cuadrado-Godia, Elisa; Bueno-Betí, Carlos; Díaz‐Ricart, Maribel; Oliveras, Anna; Novella, Susana; Gené, Gemma G.; Jung, Carole; Subirana, Isaac; Ortiz-Pérez, Josè T.; Roqué, Mercè; Freixa, Xavier; Núñez, Julio; Escolar, Ginés; Marrugat, Jaume; Hermenegildo, Carlos; Valverde, Miguel A.; Roquer, Jaume; Sanchís, Juan; Heras, Magda

doi:10.1016/j.yjmcc.2015.01.005

Cited by 40 publications

(49 citation statements)

References 35 publications

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“…Evidence suggests that activation of mononuclear cells leads to an increase of ACE2 29 and of TACE 30 , which could result in increased shedding of ACE2 from activated leukocytes. Further, levels of CD34+ cells in peripheral blood following stroke in humans may follow a similar pattern to that observed in serum ACE2 activity (Fig 2D) with an initial decrease followed by a rebound increase 31 . Taken together, these findings suggest that ACE2 shedding from brain, endothelial, and/or activated hematopoietic cells may contribute to changes in serum ACE2 activity following stroke.…”

Section: Discussionsupporting

confidence: 68%

Activation of the Neuroprotective Angiotensin-Converting Enzyme 2 in Rat Ischemic Stroke

et al. 2015

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The angiotensin converting enzyme 2/angiotensin-(1-7)/Mas axis represents a promising target for inducing stroke neuroprotection. Here, explored stroke-induced changes in expression and activity of endogenous angiotensin converting enzyme 2 and other system components in Sprague Dawley rats. To evaluate the clinical feasibility of treatments that target this axis and that may act in synergy with stroke-induced changes, we also tested the neuroprotective effects of diminazene aceturate, an angiotensin converting enzyme 2 activator, administered systemically post-stroke. Amongst rats that underwent experimental endothelin-1-induced ischemic stroke, angiotensin converting enzyme 2 activity in the cerebral cortex and striatum increased in the 24 hours after stroke. Serum angiotensin converting enzyme 2 activity was decreased within 4h post stroke, but rebounded to reach higher than baseline levels 3d post-stroke. Treatment following stroke with systemically-applied diminazene resulted in decreased infarct volume and improved neurological function without apparent increases in cerebral blood flow. Central infusion of A-779, a Mas receptor antagonist, resulted in larger infarct volumes in diminazene-treated rats, and central infusion of the angiotensin converting enzyme 2 inhibitor MLN-4760 alone worsened neurological function. The dynamic alterations of the protective angiotensin converting enzyme 2 pathway following stroke suggest that it may be a favorable therapeutic target. Indeed, significant neuroprotection resulted from post-stroke angiotensin converting enzyme 2 activation, likely via Mas signaling in a blood flow-independent manner. Our findings suggest that stroke therapeutics that target the angiotensin converting enzyme 2/angiotensin-(1-7)/Mas axis may interact cooperatively with endogenous stroke-induced changes, lending promise to their further study as neuroprotective agents.

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Section: Discussionsupporting

confidence: 68%

Activation of the Neuroprotective Angiotensin-Converting Enzyme 2 in Rat Ischemic Stroke

et al. 2015

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“…In line with previous reports we observed that the number of circulating progenitor cells including CD34 + and CD34 + /KDR + cells increases acutely following an ACS[26,27]. An early decline of EPC levels or failure to mobilize EPCs from the bone marrow have been described in ACS patients, which in turn is associated with increased mortality[26,28,29].…”

Section: Discussionsupporting

confidence: 90%

Beneficial Effects of Reconstituted High-Density Lipoprotein (rHDL) on Circulating CD34+ Cells in Patients after an Acute Coronary Syndrome

et al. 2017

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BackgroundHigh-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating progenitor cell level and function are impaired in patients with acute coronary syndrome (ACS). This study investigates the short-term effects of reconstituted HDL (rHDL) on circulating progenitor cells in patients with ACS.Methods and FindingsThe study population consisted of 33 patients with recent ACS: 20 patients from the ERASE trial (randomized to receive 4 weekly intravenous infusions of CSL-111 40 mg/kg or placebo) and 13 additional patients recruited as controls using the same enrolment criteria. Blood was collected from 16 rHDL (CSL-111)-treated patients and 17 controls at baseline and at 6–7 weeks (i.e. 2–3 weeks after the fourth infusion of CSL-111 in ERASE). CD34+ and CD34+/kinase insert domain receptor (KDR+) progenitor cell counts were analyzed by flow cytometry. We found preserved CD34+ cell counts in CSL-111-treated subjects at follow-up (change of 1.6%), while the number of CD34+ cells was reduced (-32.9%) in controls (p = 0.017 between groups). The level of circulating SDF-1 (stromal cell-derived factor-1), a chemokine involved in progenitor cell recruitment, increased significantly (change of 21.5%) in controls, while it remained unchanged in CSL-111-treated patients (p = 0.031 between groups). In vitro exposure to CSL-111 of early EPC isolated from healthy volunteers significantly increased CD34+ cells, reduced early EPC apoptosis and enhanced their migration capacity towards SDF-1.ConclusionsThe relative increase in circulating CD34+ cells and the low SDF-1 levels observed following rHDL infusions in ACS patients point towards a role of rHDL in cardiovascular repair mechanisms.

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“…[22] Elevation of EPCs in our study has been observed in stroke patients in another study when compared with controls, but 30 days after stroke, no significant change in EPCs was indicated. [23] In another study, the number and migratory activity of circulating EPCs were shown to have an inverse correlation with risk factors for coronary artery diseases[2] and Framingham risk factor score. [21] In Sobrino et al .…”

Section: Discussionmentioning

confidence: 99%

The role of endothelial progenitor cells in transient ischemic attack patients for future cerebrovascular events

et al. 2016

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Background:The role of endothelial progenitor cells (EPCs) in the maintenance of vascularization following ischemic brain after experimental stroke has been established. Accordingly, in this study, we evaluated the role of circulating EPCs in transient ischemic attack (TIA) patients for future cerebrovascular (CV) events.Materials and Methods:The level of circulating EPCs (staining markers: CD34, CD309) were determined using flow cytometry at 24 h after TIA in thirty consecutive patients. The EPCs level was also evaluated once in thirty healthy volunteers. Over a period of 12 months, all patients were evaluated by an experienced neurologist for recurrent TIA, stroke or death induced by CV disorders.Results:Circulating EPCs increased in patients group following the first attack of TIA when compared with controls. By analysis of covariance, cardiovascular event history, hyperlipidemia, and statin therapy remained significant independent predictors of EPCs. The mean (standard deviation) duration of follow-up was 10.5 (3.1) months (range, 2–12 months). During follow-up, a total of three patients died due to CV accident and four patients experienced again recurrent TIA. By analyzing data with Cox regression, EPC did not predict the future CV events in TIA patients.Conclusion:Increased incidence of future CV events did not occur in those patients with elevated EPCs in the first attack of TIA. The significant predicting factors of EPCs were cardiovascular event history, hyperlipidemia, and statin therapy.

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Mobilization of endothelial progenitor cells in acute cardiovascular events in the PROCELL study: Time-course after acute myocardial infarction and stroke

Cited by 40 publications

References 35 publications

Activation of the Neuroprotective Angiotensin-Converting Enzyme 2 in Rat Ischemic Stroke

Activation of the Neuroprotective Angiotensin-Converting Enzyme 2 in Rat Ischemic Stroke

Beneficial Effects of Reconstituted High-Density Lipoprotein (rHDL) on Circulating CD34+ Cells in Patients after an Acute Coronary Syndrome

The role of endothelial progenitor cells in transient ischemic attack patients for future cerebrovascular events

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