FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4285299995> ?p ?o ?g. }

• W4285299995 endingPage "4430" @default.
• W4285299995 startingPage "4415" @default.
• W4285299995 abstract "Background and Purpose: Myocardial infarction (MI) in diabetic patients results in higher mortality and morbidity. We and others have previously shown that bone marrow-endothelial progenitor cells (EPCs) promote cardiac neovascularization and attenuate ischemic injury. Lately, small extracellular vesicles (EVs) have emerged as major paracrine effectors mediating the benefits of stem cell therapy. Modest clinical outcomes of autologous cell-based therapies suggest diabetes-induced EPC dysfunction and may also reflect their EV derivatives. Moreover, studies suggest that post-translational histone modifications promote diabetes-induced vascular dysfunctions. Therefore, we tested the hypothesis that diabetic EPC-EVs may lose their post-injury cardiac reparative function by modulating histone modification in endothelial cells (ECs). Methods: We collected EVs from the culture medium of EPCs isolated from non-diabetic (db/+) and diabetic (db/db) mice and examined their effects on recipient ECs and cardiomyocytes in vitro, and their reparative function in permanent ligation of left anterior descending (LAD) coronary artery and ischemia/reperfusion (I/R) myocardial ischemic injuries in vivo. Results: Compared to db/+ EPC-EVs, db/db EPC-EVs promoted EC and cardiomyocyte apoptosis and repressed tube-forming capacity of ECs. In vivo, db/db EPC-EVs depressed cardiac function, reduced capillary density, and increased fibrosis compared to db/+ EPC-EV treatments after MI. Moreover, in the I/R MI model, db/+ EPC-EV-mediated acute cardio-protection was lost with db/db EPC-EVs, and db/db EPC-EVs increased immune cell infiltration, infarct area, and plasma cardiac troponin-I. Mechanistically, histone 3 lysine 9 acetylation (H3K9Ac) was significantly decreased in cardiac ECs treated with db/db EPC-EVs compared to db/+ EPC-EVs. The H3K9Ac chromatin immunoprecipitation sequencing (ChIP-Seq) results further revealed that db/db EPC-EVs reduced H3K9Ac level on angiogenic, cell survival, and proliferative genes in cardiac ECs. We found that the histone deacetylase (HDAC) inhibitor, valproic acid (VPA), partly restored diabetic EPC-EV-impaired H3K9Ac levels, tube formation and viability of ECs, and enhanced cell survival and proliferative genes, Pdgfd and Sox12, expression. Moreover, we observed that VPA treatment improved db/db EPC-mediated post-MI cardiac repair and functions. Conclusions: Our findings unravel that diabetes impairs EPC-EV reparative function in the ischemic heart, at least partially, through HDACs-mediated H3K9Ac downregulation leading to transcriptional suppression of angiogenic, proliferative and cell survival genes in recipient cardiac ECs. Thus, HDAC inhibitors may potentially be used to restore the function of diabetic EPC and other stem cells for autologous cell therapy applications." @default.
• W4285299995 created "2022-07-14" @default.
• W4285299995 creator A5010003697 @default.
• W4285299995 creator A5012532104 @default.
• W4285299995 creator A5018038423 @default.
• W4285299995 creator A5024396516 @default.
• W4285299995 creator A5031029476 @default.
• W4285299995 creator A5041230019 @default.
• W4285299995 creator A5048332870 @default.
• W4285299995 creator A5059275940 @default.
• W4285299995 creator A5060437129 @default.
• W4285299995 creator A5063830487 @default.
• W4285299995 creator A5064083898 @default.
• W4285299995 creator A5071738730 @default.
• W4285299995 creator A5075089696 @default.
• W4285299995 creator A5075648082 @default.
• W4285299995 creator A5075899752 @default.
• W4285299995 creator A5077000029 @default.
• W4285299995 creator A5078704965 @default.
• W4285299995 creator A5090449188 @default.
• W4285299995 date "2022-01-01" @default.
• W4285299995 modified "2023-10-17" @default.
• W4285299995 title "Diabetes impairs cardioprotective function of endothelial progenitor cell-derived extracellular vesicles via H3K9Ac inhibition" @default.
• W4285299995 cites W2010065060 @default.
• W4285299995 cites W2044003590 @default.
• W4285299995 cites W2058095177 @default.
• W4285299995 cites W2063109078 @default.
• W4285299995 cites W2073965098 @default.
• W4285299995 cites W2091312561 @default.
• W4285299995 cites W2095626300 @default.
• W4285299995 cites W2097742361 @default.
• W4285299995 cites W2098667235 @default.
• W4285299995 cites W2143658931 @default.
• W4285299995 cites W2149204225 @default.
• W4285299995 cites W2161982738 @default.
• W4285299995 cites W2164232024 @default.
• W4285299995 cites W2176907465 @default.
• W4285299995 cites W2235604943 @default.
• W4285299995 cites W2252804625 @default.
• W4285299995 cites W2293182033 @default.
• W4285299995 cites W2293907058 @default.
• W4285299995 cites W2414777237 @default.
• W4285299995 cites W2444268874 @default.
• W4285299995 cites W2512730605 @default.
• W4285299995 cites W2522274739 @default.
• W4285299995 cites W2560195968 @default.
• W4285299995 cites W2590079466 @default.
• W4285299995 cites W2590541838 @default.
• W4285299995 cites W2599464159 @default.
• W4285299995 cites W2738411868 @default.
• W4285299995 cites W2739174192 @default.
• W4285299995 cites W2746108841 @default.
• W4285299995 cites W2757238590 @default.
• W4285299995 cites W2766634454 @default.
• W4285299995 cites W2888798518 @default.
• W4285299995 cites W2904770603 @default.
• W4285299995 cites W2924894870 @default.
• W4285299995 cites W2939354927 @default.
• W4285299995 cites W2944544314 @default.
• W4285299995 cites W2962383654 @default.
• W4285299995 cites W2966010975 @default.
• W4285299995 cites W2967657641 @default.
• W4285299995 cites W2979122122 @default.
• W4285299995 cites W2993198898 @default.
• W4285299995 cites W3009818378 @default.
• W4285299995 cites W3024075488 @default.
• W4285299995 cites W3086620859 @default.
• W4285299995 cites W3161545822 @default.
• W4285299995 doi "https://doi.org/10.7150/thno.70821" @default.
• W4285299995 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35673580" @default.
• W4285299995 hasPublicationYear "2022" @default.
• W4285299995 type Work @default.
• W4285299995 citedByCount "5" @default.
• W4285299995 countsByYear W42852999952023 @default.
• W4285299995 crossrefType "journal-article" @default.
• W4285299995 hasAuthorship W4285299995A5010003697 @default.
• W4285299995 hasAuthorship W4285299995A5012532104 @default.
• W4285299995 hasAuthorship W4285299995A5018038423 @default.
• W4285299995 hasAuthorship W4285299995A5024396516 @default.
• W4285299995 hasAuthorship W4285299995A5031029476 @default.
• W4285299995 hasAuthorship W4285299995A5041230019 @default.
• W4285299995 hasAuthorship W4285299995A5048332870 @default.
• W4285299995 hasAuthorship W4285299995A5059275940 @default.
• W4285299995 hasAuthorship W4285299995A5060437129 @default.
• W4285299995 hasAuthorship W4285299995A5063830487 @default.
• W4285299995 hasAuthorship W4285299995A5064083898 @default.
• W4285299995 hasAuthorship W4285299995A5071738730 @default.
• W4285299995 hasAuthorship W4285299995A5075089696 @default.
• W4285299995 hasAuthorship W4285299995A5075648082 @default.
• W4285299995 hasAuthorship W4285299995A5075899752 @default.
• W4285299995 hasAuthorship W4285299995A5077000029 @default.
• W4285299995 hasAuthorship W4285299995A5078704965 @default.
• W4285299995 hasAuthorship W4285299995A5090449188 @default.
• W4285299995 hasBestOaLocation W42852999951 @default.
• W4285299995 hasConcept C111566952 @default.
• W4285299995 hasConcept C126322002 @default.
• W4285299995 hasConcept C201750760 @default.
• W4285299995 hasConcept C2778198053 @default.

• next