tbuckley/cabot-search huggingface dataset:
Abstract 293: Oxidative Stress in Obese Mice and Potential Melatonin Cardioprotective Effects
Authors: Rita Rezzani, Gaia Favero, Alessandra Stacchiotti, Francesca Bonomini, Luigi F Rodella
Journal: Circulation Research (2018)

Adult obesity is a worldwide pandemic condition that leads to the metabolic syndrome and a spectrum of irreversible cardiovascular, neurological, renal and digestive morbidities and cardiovascular diseases represent the leading cause of death in obese people. Cardiomyocytes are particularly sensitive to oxidative damage due to the link between mitochondria and sarcoplasmic reticulum necessary for calcium flux and contraction. Melatonin, versatile and pleiotropic indoleamine with multiple actions, has also important cardioprotective properties. The present study defined mitochondria cardiomyocyte changes and relative oxidative stress pattern in ob/ob mice treated orally or not with melatonin at 100 mg/kg/day for 8 weeks. We observed that ob/ob mice mitochondria in cardiomyocytes sub-sarcolemmal and inter-myofibrillar compartments are often devoid of cristae and have an abnormal large size, so they are defined mega-mitochondria. Moreover, in ob/ob mice, we observed also alteration of peroxisome proliferator-activated receptor gamma coactivator-1α, protein that controls mitochondrial biogenesis, oxidative metabolism and inflammation, together with a deregulated endogenous antioxidant system, showing in particular altered heme oxygenase-1 cardyomiocyte expression. Melatonin oral treatment in ob/ob mice restores heart mitochondria and minimizes oxidative stress and inflammation. These preliminary data indicate a significant protective role of melatonin supplementation against obesity-related heart alterations.
Abstract 438: Familial Cardiomyopathy Mutations Affect Mechanosensing at the Molecular and Cellular Levels
Authors: Sarah Clippinger, Paige Cloonan, Lina Greenberg, Tom Stump, Michael J Greenberg
Journal: Circulation Research (2018)

Familial cardiomyopathies are the leading cause of sudden cardiac death in young people, affecting more than 1 in 500 people. Two common forms, hypertrophic (HCM) and dilated (DCM) cardiomyopathies, are characterized by remodeling of the heart tissue, frequently accompanied by fibrosis and myocyte disarray. These diseases are primarily caused by mutations in sarcomeric proteins that regulate the contraction of the heart; however, it is not clear how these point mutations at the molecular level lead to the disease phenotype seen in patients. To better understand this process, we have examined the molecular and cellular consequences of two mutations in troponin T, R92Q and ΔK210, that cause HCM and DCM, respectively. Using recombinant proteins and a battery of in vitro biochemical and biophysical techniques, we find that R92Q increases activation of the thin filament by stabilizing myosin force generating states while ΔK210 reduces the ability of myosin to access these states at submaximal calcium levels. To study these mutations at the single cell level, we used CRISPR/Cas9 to generate human stem cell derived cardiomyocytes bearing these mutations. We examined the structural and contractile properties of single cells on engineered hydrogels that mimic either healthy or diseased hearts. Consistent with our molecular studies, we find that R92Q causes increased force production and power output. Interestingly, the ΔK210 mutation does not affect cellular force or power output on substrates that mimic the stiffness of the healthy heart, but it causes disordering of the sarcomeres on stiff substrates. This suggests a mechanism for ΔK210 where fibrosis leads to progressive loss of contractile function via mechanosensitive structural remodeling. Taken together, these results (1) demonstrate that alterations in force production and mechanosensing contribute to the disease pathogenesis in familial cardiomyopathies and (2) illuminate the differential mechanisms that lead to either HCM or DCM.
BIOMECHANICS OF THE REDUCED LEAFLET MOTION AND THROMBOSIS AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Jean Louis Sablayrolles, Sanjeet Singh Avtaar Singh, David Attias, Laura Mazzocchi, Simone Morganti, Christos G. Mihos, Ferdinando Auricchio, Francesco Nappi
Journal: Journal of the American College of Cardiology (2019)
In Vivo Eradication of a Rituximab-Resistant Human CD20+ B Cell Lymphoma by Rituximab-CpG Oligodeoxynucleotide Conjugate Is Mediated by Natural Killer Cells and Complement.
Authors: David J Betting, Kamran Kafi, Reiko E Yamada, Kristopher K Steward, Tove Olafsen, Anna M Wu, Nico van Rooijen, John M Timmerman
Journal: Blood (2009)
Immunomodulatory Effects of HDACi in Combination with Checkpoint Blockade and Lenalidomide in the Immunosuppressive Multiple Myeloma Bone Marrow Microenvironment
Authors: Greg D Whitehill, Alicia Chivers, Bryan Danielson, Julien Sr Tessier, Gabriela Hernandez Duran, Gabrielle L Bender, Douglas W. Sborov, Craig C Hofmeister, James Bradner, Teru Hideshima, Kenneth C Anderson, Gullu Gorgun
Journal: Blood (2017)
PREVALENCE OF NON-TRAUMATIC INTRACEREBRAL HEMORRHAGE ASSOCIATED WITH POSSIBLE OR PROBABLE CEREBRAL AMYLOID ANGIOPATHY AMONG PATIENTS WITH ATRIAL FIBRILLATION ON ANTICOAGULATION
Authors: Robert Ward, Shiva Ponamgi, Stephen English, Christopher DeSimone, Alejandro Rabinstein, Jonathan Graff-Radford, Samuel Asirvatham, David Holmes
Journal: Journal of the American College of Cardiology (2019)
Integration of transcriptional and mutational data simplifies the stratification of peripheral T‐cell lymphoma
Authors: Francesco Maura, Luca Agnelli, Daniel Leongamornlert, Niccolò Bolli, Wing C. Chan, Anna Dodero, Cristiana Carniti, Tayla B. Heavican, Alessio Pellegrinelli, Giancarlo Pruneri, Adam Butler, Shriram G. Bhosle, Annalisa Chiappella, Alice Di Rocco, Pier Luigi Zinzani, Francesco Zaja, Roberto Piva, Giorgio Inghirami, Wenyi Wang, Teresa Palomero, Javeed Iqbal, Antonino Neri, Peter J. Campbell, Paolo Corradini
Journal: American Journal of Hematology (2019)

The histological diagnosis of peripheral T-cell lymphoma (PTCL) can represent a challenge, particularly in the case of closely related entities such as angioimmunoblastic T-lymphoma (AITL), PTCL-not otherwise specified (PTCL-NOS), and ALK-negative anaplastic large-cell lymphoma (ALCL). Although gene expression profiling and next generations sequencing have been proven to define specific features recurrently associated with distinct entities, genomic-based stratifications have not yet led to definitive diagnostic criteria and/or entered into the routine clinical practice. Herein, to improve the current molecular classification between AITL and PTCL-NOS, we analyzed the transcriptional profiles from 503 PTCLs stratified according to their molecular configuration and integrated them with genomic data of recurrently mutated genes (RHOA G17V , TET2, IDH2 R172 , and DNMT3A) in 53 cases (39 AITLs and 14 PTCL-NOSs) included in the series. Our analysis unraveled that the mutational status of RHOA G17V , TET2, and DNMT3A poorly correlated, individually, with peculiar transcriptional fingerprints. Conversely, in IDH2 R172 samples a strong transcriptional signature was identified that could act as a surrogate for mutational status. The integrated analysis of clinical, mutational, and molecular data led to a simplified 19-gene signature that retains high accuracy in differentiating the main nodal PTCL entities. The expression levels of those genes were confirmed in an independent cohort profiled by RNA-sequencing.
CONCOMITANT PULMONARY VEIN ISOLATION AND LEFT ATRIAL APPENDAGE OCCLUSION FOR ATRIAL FIBRILLATION: A META-ANALYSIS OF SAFETY AND EFFICACY OUTCOMES
Authors: Abhishek Thandra, Aravdeep Jhand, Dinesh Reddy Apala, Raviteja Guddeti, Andrew Goldsweig, Venkata Alla
Journal: Journal of the American College of Cardiology (2019)
RETROSPECTIVE ASSESSMENTS OF INTRA- AND INTER-RATER RELIABILITY OF QUANTITATIVE FLOW RATIO
Authors: Takayuki Ishihara, Mitsuyoshi Takahara, Takuya Tsujimura, Naoya Kurata, Osamu Iida, Mitsutoshi Asai, Masaharu Masuda, Shin Okamoto, Kiyonori Nanto, Takashi Kanda, Shota Okuno, Yasuhiro Matsuda, Hiroyuki Kawai, Aki Tsuji, Yosuke Hata, Hiroyuki Uematsu, Yuki Sato, Taku Toyoshima, Naoko Higashino, Toshiaki Mano
Journal: Journal of the American College of Cardiology (2019)
INCIDENCE, CHARACTERISTICS, AND CLINICAL IMPLICATIONS OF LEFT ATRIAL CALCIFICATION ON CARDIAC COMPUTED TOMOGRAPHY IN PATIENTS UNDERWENT MITRAL VALVE SURGERY
Authors: Jah Yeon Choi, Chi Young Shim, Young-Ju Seo, Young Jin Kim, Kang-Un Choi, Geu-Ru Hong, Jong-Won Ha
Journal: Journal of the American College of Cardiology (2019)
Evidence for Urban–Rural Disparity in Temperature–Mortality Relationships in Zhejiang Province, China
Authors: Kejia Hu, Yuming Guo, Stefan Hochrainer-Stigler, Wei Liu, Linda See, Xuchao Yang, Jieming Zhong, Fangrong Fei, Feng Chen, Yunquan Zhang, Qi Zhao, Gongbo Chen, Qian Chen, Yizhe Zhang, Tingting Ye, Lu Ma, Shanshan Li, Jiaguo Qi
Journal: Environmental Health Perspectives (2019)

Background: Temperature-related mortality risks have mostly been studied in urban areas, with limited evidence for urban–rural differences in the temperature impacts on health outcomes. Objectives: We investigated whether temperature–mortality relationships vary between urban and rural counties in China. Methods: We collected daily data on 1 km gridded temperature and mortality in 89 counties of Zhejiang Province, China, for 2009 and 2015. We first performed a two-stage analysis to estimate the temperature effects on mortality in urban and rural counties. Second, we performed meta-regression to investigate the modifying effect of the urbanization level. Stratified analyses were performed by all-cause, nonaccidental (stratified by age and sex), cardiopulmonary, cardiovascular, and respiratory mortality. We also calculated the fraction of mortality and number of deaths attributable to nonoptimum temperatures associated with both cold and heat components. The potential sources of the urban–rural differences were explored using meta-regression with county-level characteristics. Results: Increased mortality risks were associated with low and high temperatures in both rural and urban areas, but rural counties had higher relative risks (RRs), attributable fractions of mortality, and attributable death counts than urban counties. The urban–rural disparity was apparent for cold (first percentile relative to minimum mortality temperature), with an RR of 1.47 [95% confidence interval (CI): 1.32, 1.62] associated with all-cause mortality for urban counties, and 1.98 (95% CI: 1.87, 2.10) for rural counties. Among the potential sources of the urban–rural disparity are age structure, education, GDP, health care services, air conditioners, and occupation types. Conclusions: Rural residents are more sensitive to both cold and hot temperatures than urban residents in Zhejiang Province, China, particularly the elderly. The findings suggest past studies using exposure–response functions derived from urban areas may underestimate the mortality burden for the population as a whole. The public health agencies aimed at controlling temperature-related mortality should develop area-specific strategies, such as to reduce the urban–rural gaps in access to health care and awareness of risk prevention. Future projections on climate health impacts should consider the urban–rural disparity in mortality risks. https://doi.org/10.1289/EHP3556
TESTOSTERONE AND SEX HORMONE-BINDING GLOBULIN IN DYSGLYCEMIC WOMEN AT HIGH CARDIOVASCULAR RISK: A REPORT FROM THE OUTCOME REDUCTION WITH AN INITIAL GLARGINE INTERVENTION TRIAL
Authors: Anne Wang, Stefan Arver, Kurt Boman, Hertzel Gerstein, Sibylle Hess, Shun Fu Lee, Lars Ryden, Linda Mellbin
Journal: Journal of the American College of Cardiology (2019)
DOES ORIENTING SAPIEN3 DURING CRIMPING IN TAVR AFFECT FINAL ORIENTATION TO CORONARIES TO IMPACT CORONARY REACCESS? A PILOT STUDY
Authors: Gilbert Hin-Lung Tang, Syed Zaid, Nish Patel, Eisha Gupta, Hasan Ahmad, Asaad Khan, Jason Kovacic, Cenap Undemir, Joshua B. Goldberg, Muhammad Khan, Steven Lansman, George Dangas, Samin Sharma, Annapoorna Kini
Journal: Journal of the American College of Cardiology (2019)
ALBUMINURIA AS A LONG-TERM PREDICTOR OF CARDIOVASCULAR EVENTS AMONG PATIENTS WITH DIABETES AND CORONARY ARTERY DISEASE: MASS REGISTRY INSIGHTS
Authors: Eduardo Gomes Lima, Whady Hueb, Jaime Linhares Filho, Daniel Valente Batista, Rafael Silva, Eduardo Martins, Diogo Freitas Cardoso Azevedo, Paulo Rezende, Jose Ramires, Roberto Kalil-Filho
Journal: Journal of the American College of Cardiology (2019)
Abstract 15829: Hybrid Coronary Revascularization versus Multivessel Pci-Stenting: A Propensity Match Analysis
Authors: Alberto Repossini, Maurizio Tespili, Lorenzo Di Bacco, Antonio Saino, Laura Giroletti, Claudio Muneretto
Journal: Circulation (2015)

Introduction: Despite current guidelines and the proven LIMA-LAD superiority, PCI-stenting is still largely performed in patients with multi-vessel coronary disease (MVD). Hypothesis: We investigated the role of hybrid revascularization (HCR) meaning MIDCAB combined with PCI as a planned strategy and compared it with PCI alone in patients with multi-vessel coronary disease involving proximal LAD. Methods: We retrospectively analyzed 605 patients with MVD: 179 hybrid and 426 multi-vessel PCI revascularizations. All patients have been discussed within the heart team, based on pre-operative risk (Logistic EuroSCORE II) and on coronary lesions complexity (SYNTAX score). A propensity score matching has been performed and 127 patients from each series selected. Early results were evaluated, and survival analysis for all-causes mortality, cardiac death and MACCE were performed. Results: One-hundred forty-two patients (142/254) had two-vessel disease and 78/254 (41 HCR and 37 PCI patients) had left main involvement. 28 LAD total occlusion in HCR and 18 in PCI groups. 20 PCI patients had recent STEMI and 25 HCR patients. Mean SYNTAX score was 27.5±3.5 and 27±4.0 in HCR and PCI (p=0.8) respectively. No hospital mortality was reported. Overall survival rate at 60 months was (HCR 95% CI: 84.8%, 80.6-91% vs PCI 78.7%, 72.1-85.3%, p=0.23). Freedom from cardiac death survival rate at 60 months was (HCR 95% CI: 91.4%, 85.8-97% vs PCI 84.5%, 78.1-90.9%, p=0.33). Freedom from MACCE survival rate at 60 months was better in HCR group than PCI (95% CI: 74.5%, 66.8-82.4% vs 54.4%, 46.6-62.2%, p=0.015). The reduced target vessel revascularization rate in HCR group was due to LAD repeated revascularization in PCI group. Conclusions: Hybrid Coronary revascularization is a safe and effective strategy to achieve a complete revascularization in patients with multi-vessel disease. HCR, reducing SYNTAX score when due to LAD lesions and the number of stents used to complete revascularization, improved results of PCI-stenting in patients with MVD providing a significantly better freedom from MACCE at mid-term.
MULTIPARAMETRIC CARDIAC MAGNETIC RESONANCE PHENOTYPING OF PATIENTS WITH A HISTORY OF CARDIAC TRANSPLANT REJECTION
Authors: Robert J.H. Miller, Andriana Nikolova, Alan Kwan, Ryan Levine, Sadia Dimbil, Jon Kobashigawa, Evan Kransdorf, Jignesh Patel, Louise Thomson, Debiao Li, Daniel Berman, Balaji Tamarappoo
Journal: Journal of the American College of Cardiology (2019)
Topotecan-vincristine-doxorubicin in metastatic neuroblastoma with insufficient response to rapid COJEC: Results of a SIOPEN Group study.
Authors: Loredana Amoroso, Dominique Valteau-Couanet, Victoria Castel, Penelope Brock, Andrew DJ Pearson, Ruth Lydia Ladenstein, Alberto Garaventa
Journal: Journal of Clinical Oncology (2013)

10016 Background: This study evaluated the activity and toxicity of a topotecan-vincristine-doxorubicin (TVD) combination administered to patients with stage 4 neuroblastoma failing to achieve adequate metastatic remission after induction therapy (rapid COJEC) according to the HR-NBL-1 SIOPEN protocol. Methods: Patients above 1 year of age with stage 4 neuroblastoma, who failed to achieve adequate metastatic remission with rapid COJEC were eligible. Topotecan was administered at 1.5 mg/m²/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m² and doxorubicin, 45 mg/m². Tumour response was assessed after 2 TVD courses, according to the INSS criteria. Patients achieving CR or VGPR (metastatic CR) or PR (≤ 3 skeletal MIBG spots and cytomorphological CR on 2 bone marrow aspirates) underwent myeloablative therapy (MAT) followed by PBSC rescue. Patients who failed to achieve PR after 2-4 TVD courses, or developed PD were withdrawn from the study and were treated at physicians’ discretion. Results were recorded in the SIOPEN-R-NET database. Results: Sixty-eight patients who did not achieve CR or VPGR after rapid COJEC were enrolled in the study. Responses of 68 assessable patients after 2 TVD courses included 4 CR, 13 VPGR, 26 PR, 7 MR, 14 NR, 2 PD, 2 missing data (major response rate 65 %). Twenty-five patients who achieved CR or VGPR or PR (metastatic CR) received MAT according to protocol. Thirty-three/68 patients are presently alive, no toxic deaths occurred. Toxicity was mostly hematopoietic. Fifty-three patients experienced grade 4 neutropenia, 47 grade 4 thrombocytopenia and 12 grade 4 anemia after the first course. Forty-nine patients developed grade 4 neutropenia, 41 grade 4 thrombocytopenia and 12 grade 4 anemia after the second course. Twenty-six patients required hospitalisation for systemic antibiotic therapy after the first course, and 19 patients after the second. Grade 3-4 stomatitis requiring a liquid diet or TPN was observed in 17 patients after the first cycle and 9 after the second. Conclusions: This TVD combination was active and tolerable in patients with metastatic neuroblastoma after treatment with rapid COJEC. Clinical trial information: 2006-001489-17.
TISSUE TRACKING CT MYOCARDIAL STRAIN IN PATIENTS WITH ABNORMAL CORONARY CALCIUM SCORE
Authors: Erasmo De La Pena-Almaguer, José Gildardo Paredes-Vázquez, Luis Gerardo Tellez, Mariana Vanoye-Tamez, Marcelo García-Pablos, Vicente Jimenez Franco
Journal: Journal of the American College of Cardiology (2019)
RELATIONSHIP BETWEEN LENGTH OF HOSPITAL STAY AND 3-YEAR OUTCOMES AFTER LEFT MAIN REVASCULARIZATION: THE EXCEL TRIAL
Authors: Jaya Chandrasekhar, Adrian Banning, David Taggart, Roxana Mehran, Zixuan Zhang, Ori Ben-Yehuda, Ovidiu Dressler, A. Kappetein, Patrick Serruys, Joseph Sabik, Gregg Stone
Journal: Journal of the American College of Cardiology (2019)
HAP1 loss confers l-asparaginase resistance in ALL by downregulating the calpain-1-Bid-caspase-3/12 pathway
Authors: Jung Kwon Lee, SungMyung Kang, Xidi Wang, Jesusa L. Rosales, Xu Gao, Hee-Guk Byun, Yan Jin, Songbin Fu, Jinghua Wang, Ki-Young Lee
Journal: Blood (2019)
LISTING OLDER PATIENTS FOR TRANSPLANT OR OFFERING LVAD DESTINATION THERAPY?
Authors: Anuradha (Anu) Lala-Trindade, John Rowland, Bart Ferket, Marissa Miller, Francis Pagani, Emilia Bagiella, Alan Moskowitz, Sean Pinney, Annetine Gelijns, Donna Mancini
Journal: Journal of the American College of Cardiology (2019)
ATM activation is a marker of cellular aging and a precursor to replicative senescence.
Authors: Christopher J. Bakkenist, Rachid Drissi, Jing Wu, Michael B. Kastan, Jeffrey S. Dome
Journal: Cancer Research (2004)

2405  Replicative senescence is a natural barrier to cellular proliferation that is triggered by telomere erosion and dysfunction. Although it is recognized that the p53 and Rb pathways are critical for the induction and maintenance of replicative senescence, little is known about the sensors of telomere dysfunction that initiate the senescence response. ATM, the product of the gene that is mutated in the disorder ataxia telangiectasia, plays a critical role in the initiation of response pathways to ionizing radiation (IR). To assess whether ATM is activated during cellular aging and senescence, we used antibodies that specifically recognize the active, phosphorylated form of ATM. We found that whereas activated ATM was rarely observed in early-passage human fibroblasts, it was readily detected in late-passage fibroblasts. The ATM activation in late-passage cells was accompanied by accumulation of total p53 and p21 proteins and the formation of nuclear foci that contain phosphorylated ATM, NBS1, 53BP1, and H2AX-γ. Ectopic expression of telomerase in late-passage fibroblasts abrogated ATM activation, suggesting that the ATM activation resulted from telomere dysfunction. To ascertain whether telomere dysfunction-induced ATM activation requires chromosomal fusion-bridge-breakage cycles, we uncapped telomeres in quiescent, non-dividing cells using a lentivirus that expresses a dominant-inhibitory form of the telomere binding protein TRF2 (TRF2ΔBΔM). Transduction of TRF2ΔBΔM, but not a control TRF2 construct, into non-cycling cells activated ATM, indicating that telomere uncapping per se is sufficient for ATM activation. Although ATM activation was readily observed in pre-senescent cells, it disappeared with progression to senescence. However, ATM had the ability to be activated in senescent cells in response to IR, suggesting that the short telomeres of senescent cells are somehow shielded from initiating a signaling response. Together, these results are consistent with the idea that ATM activation contributes to the induction, but not the maintenance, of replicative senescence.
SERIAL HIGH-SENSITIVITY CARDIAC TROPONIN T MEASUREMENTS TO RULE OUT ACUTE MYOCARDIAL INFARCTION AND A SINGLE HIGH BASELINE MEASUREMENT FOR SWIFT RULE-IN: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Murat Arslan, Admir Dedic, Eric Boersma, Eric A. Dubois
Journal: Journal of the American College of Cardiology (2019)
Abstract 216: Interleukin-10 Deficiency Impairs Reparative Properties of Bone Marrow-Derived Endothelial Progenitor Cell Exosomes
Authors: Yujia Yue, Venkata N Garikipati, Yan Tang, Maria Cimini, Zhongjian Cheng, Chunlin Wang, May Troungcao, Raj Kishore
Journal: Circulation Research (2018)

EPC based therapy in clinical trials is largely benefited from paracrine effect such as exosomes. Exosomes mirror the behavior of parental cells and their function is dependent on RNAs and proteins packed inside. Systemic inflammation in MI patients greatly compromise the reparative performance of EPCs and relative exosomes. We hypothesized that EPCs under inflammatory stress produce dysfunctional exosomes with altered content, which compromise EPCs reparative benefit in ischemic heart disease. We choose interleukin-10 knockout (IL-10KO) mice as a model mimicking systemic inflammation. After EPC isolation and expansion from IL-10KO and wild-type (WT) mice, we isolated exosomes and compared their reparative properties both in vitro and in vivo . Our in vitro studies showed WT-EPC-Exo treatment enhanced endothelial cell proliferation and tube formation, and inhibited apoptosis, whereas IL-10KO-Exo exhibited impaired or even detrimental effects. We used MI mouse model to compare the in vivo function of two groups of exosomes, we found WT-EPC-Exo treatment significantly improved left ventricle cardiac function, inhibited cell death and promoted angiogenesis; while these benefits were lost in IL-10KO-EPC-Exo treated group. Both in vitro and in vivo studies suggested impaired exosome function under IL-10 deficiency. We checked the alteration of exosomal content using NGS RNAseq and mass spectrometry and found the RNA and protein expression pattern is drastically different in two groups of exosomes. Importantly, IL-10KO-EPC-Exo were highly enriched in microRNAs and proteins that promote inflammation and apoptosis and inhibit angiogenesis. We picked two candidates for further study, mir-375 and integrin linked kinase (ilk), both are highly enriched in IL-10KO-EPC-Exo. Through modulating the expression of mir-375 and ilk in exosomes, we partially rescued IL-10KO-EPC-Exo dysfunction. Thus, our study revealed that even the same type of cells, under different conditions, secrete exosomes with different function. The differences in exosomal function is caused by alteration in exosomal content, and the function can be enhanced or rescued by modulating specific targets in exosomes.