244 research outputs found
Effect of gender on reason for hospitalization and mortality in critical care : observational study
No full textPurified exosomes from human cardiac progenitor cells improve cardiac function after myocardial infarction in vivo
No full textBackground: Cardiac progenitor cell (CPC) transplantation improves cardiac function after myocardial infarction. Exosomes (Exo) are secreted nano-sized membrane vesicles that act as intercellular carriers of proteins and RNAs. Here, we investigated the role of Exo in the paracrine secretion by human CPCs (Exo-CPC), as compared to those from normal human fibroblasts (Exo-NHDF).
Methods: CPC were derived from atrial explants of patients who underwent heart valve surgery. Exo were precipitated with ExoQuickTM. Cytoprotective and proangiogenic assays were performed with mouse cardiomyocytes (CM) and human
endothelial cells (HUVEC), respectively. The in vivo effects of Exo- CPC and Exo-NHDF were tested in a rat model of acute myocardial infarction.
Results: In vitro, Exo- CPC significantly reduced starvation-induced CM apoptosis by 59% (p<0.05), whereas Exo-NHDF did not. They also stimulated tube formation by HUVEC in Matrigel (total tube length 7912.38±1076 a.u.) compared with Exo-NHDF (total tube length 5095.25±747 a.u.; p<0.05). When injected into infarcted rat hearts, Exo-CPC, but not Exo-NHDF, significantly reduced infarct scar (0.58±0.08 a.u. vs. Exo-NHDF, 0.76±0.01 a.u.; p<0.05) while increasingnew vessel formation (84±13 vs. 34±5 vessels/mm2; p<0.01). Left ventricular ejection fraction decreased from baseline to 7 days in hearts injected with PBS (-21.3±4.5%) or Exo-NHDF (-12±6.3%) but was maintained in those injected with Exo-CPC (+0.8±6.8%; p<0.05 vs. PBS).
Conclusions: Exo accounts for proangiogenic and antiapoptotic activities of human CPCs. Exo-CPC injected into infarcted hearts improves cardiac function early after MI. As a cell-free product, Exo-CPC has a potential for circumventing many of the limitations of cell therapy for cardiac repair
Edoxaban and/or colchicine in outpatients with COVID-19: rationale and design of the CONVINCE trial.
No full textBACKGROUND
An excessive inflammatory response and a hypercoagulable state are not infrequent in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse clinical outcomes. However, the optimal treatment strategy for COVID-19 patients managed in the out-of-hospital setting is still uncertain.
DESIGN
The CONVINCE (NCT04516941) is an investigator-initiated, open-label, blinded-endpoint, 2 × 2 factorial design randomized trial aimed at assessing two independently tested hypotheses (anticoagulation and anti-inflammatory ones) in COVID-19 patients. Adult symptomatic patients (≥18 years of age) within 7 days from reverse transcription-PCR (RT-PCR) diagnosis of SARS-CoV-2 infection managed at home or in nursery settings were considered for eligibility. Eligible patients fulfilling all inclusion and no exclusion criteria were randomized to edoxaban versus no treatment (anticoagulation hypothesis) and colchicine versus no treatment (anti-inflammatory hypothesis) in a 1 : 1:1 : 1 ratio. The study had two co-primary endpoints (one for each randomization), including the composite of major vascular thrombotic events at 25 ± 3 days for the anticoagulation hypothesis and the composite of SARS-CoV-2 detection rates at 14 ± 3 days by RT-PCR or freedom from death or hospitalizations (anti-inflammatory hypothesis). Study endpoints will be adjudicated by a blinded Clinical Events Committee. With a final sample size of 420 patients, this study projects an 80% power for each of the two primary endpoints appraised separately.
CONCLUSION
The CONVINCE trial aims at determining whether targeting anticoagulation and/or anti-inflammatory pathways may confer benefit in COVID-19 patients managed in the out-of-hospital setting.
TRIAL REGISTRATION
ClinicalTrials.gov number, NCT04516941
Exosomes secreted by human cardiac progenitors contain micro-RNA with cardioprotective and pro-angiogenic activities
No full textReal-time 3-dimensional transesophageal echocardiography during double percutaneous mitral edge-to-edge procedure
No full textExosomes secreted by adult human cardiac progenitor cells inhibit cardiomyocyte apoptosis, stimulate angiogenesis, and improve cardiac function after myocardial infarction
No full textExosomes from human cardiac progenitor cells, but not those from patient-matched bone marrow-derived mesenchymal stem cells,improve cardiac function after myocardial infarction in vivo
No full textBackground: Both human cardiac progenitor cells (CPC) and bone marrow-derived mesenchymal stem cells (MSC) have been tested in clinical trials of cell transplantation in patients with myocardial infarction (MI). We have recently shown that Exosomes (secreted nanovesicles; Exo) from CPC account for cardioprotective and proangiogenic activities of these cells both in vitro and in vivo. This study aimed to compare Exo-CPC and Exo-MSC in terms of cardioprotective effects and functional improvement after MI. The role of microRNA (miRNA) and ischemic preconditioning (IPC) were assessed.
Methods: CPC and MSC were derived from right atrial appendage and bone aspirate from patients undergoing heart valve surgery. Samples from both tissues were obtained for a patient-matched comparison of Exo from the two cell lines. Exo were isolated by differential ultracentrifugation of conditioned media from CPC or MSC. Anti-apoptotic and proangiogenic effects of Exo-CPC and Exo-MSC were assessed in vitro and compared with Exo from human dermal fibroblast cell line (Exo-F). IPC was performed by subjecting CPC or MSC to two short rounds of hypoxia and glucose deprivation. miRNA profiles of Exo were assessed by real-time PCR. Exo-CPC and Exo-MSC from 8 patients were injected intramyocardially in 8 rats each after permanent ligation of the left anterior descending coronary artery. Left ventricular ejection fraction (LVEF) was measured by echocardiography 1 and 4 weeks after MI.
Results: Although both Exo-CPC and Exo-MSC inhibited cardiomyocyte (CM) apoptosis after serum starvation in vitro if compared with Exo-F, Exo-CPC showed higher efficacy (21±4% Exo-CPC; 28±4% Exo-MSC; 40±5% Exo-F). IPC of Exo-producing cells further reduced numbers of apoptotic CM (17±1% Exo-CPC; 23±3% Exo-MSC). Exo-CPC, but not Exo-F, were proangiogenic in HUVEC cells. miR-210, miR132 and miR-146a were among the most highly enriched miRNA in Exo-CPC. CM transfected with miR-210 or miR-132 mimics showed increased tolerance to apoptosis, whereas siRNA specific for these miRNA had opposite effects. In vivo, LVEF was significantly improved in hearts injected with Exo-CPC compared to those injected with patient-matched Exo-MSC both at 1 week (87.0±9.9% vs 61.1±11.9; p<0.05) and 4 weeks after MI (75.4±8.9% vs 58.7±18.4%; p<0.05).
Conclusion: These results from patient-matched analyses show, for the first time, that Exo-CPC is superior to Exo-MSC at inhibiting CM apoptosis in vitro, and at improving cardiac function after MI in vivo. As a cell-free approach, Exo could streamline clinical translation of regenerative heart therapy
Transcatheter Repair of Severe Functional Tricuspid Insufficiency Using a Mitral Clip System: Transgastric Views Are the Key for an Effective Guide
No full textInflammatory extracellular vesicles prompt heart dysfunction via TRL4-dependent NF-κB activation
No full textBackground: After myocardial infarction, necrotic cardiomyocytes release damage-associated proteins that stimulate innate immune pathways and macrophage tissue infiltration, which drives inflammation and myocardial remodeling. Circulating inflammatory extracellular vesicles play a crucial role in the acute and chronic phases of ischemia, in terms of inflammatory progression. In this study, we hypothesize that the paracrine effect mediated by these vesicles induces direct cytotoxicity in cardiomyocytes. Thus, we examined whether reducing the generation of inflammatory vesicles within the first few hours after the ischemic event ameliorates cardiac outcome at short and long time points. Methods: Myocardial infarction was induced in rats that were previously injected intraperitoneally with a chemical inhibitor of extracellular-vesicle biogenesis. Heart global function was assessed by echocardiography performed at 7, 14 and 28 days after MI. Cardiac outcome was also evaluated by hemodynamic analysis at sacrifice. Cytotoxic effects of circulating EV were evaluated ex-vivo in a Langendorff, system by measuring the level of cardiac troponin I (cTnI) in the perfusate. Mechanisms undergoing cytotoxic effects of EV derived from pro-inflammatory macrophages (M1) were studied in-vitro in primary rat neonatal cardiomyocytes. Results: Inflammatory response following myocardial infarction dramatically increased the number of circulating extracellular vesicles carrying alarmins such as IL-1α, IL-1β and Rantes. Reducing the boost in inflammatory vesicles during the acute phase of ischemia resulted in preserved left ventricular ejection fraction in vivo. Hemodynamic analysis confirmed functional recovery by displaying higher velocity of left ventricular relaxation and improved contractility. When added to the perfusate of isolated hearts, post-infarction circulating vesicles induced significantly more cell death in adult cardiomyocytes, as assessed by cTnI release, comparing to circulating vesicles isolated from healthy (non-infarcted) rats. In vitro inflammatory extracellular vesicles induce cell death by driving nuclear translocation of NF-κB into nuclei of cardiomyocytes. Conclusion: Our data suggest that targeting circulating extracellular vesicles during the acute phase of myocardial infarction may offer an effective therapeutic approach to preserve function of ischemic heart
- …
