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01.12.2023 | Original Contribution

Anti-angiogenic effect of exo-LncRNA TUG1 in myocardial infarction and modulation by remote ischemic conditioning

verfasst von: Yini Dang, Wenjie Hua, Xintong Zhang, Hao Sun, Yingjie Zhang, Binbin Yu, Shengrui Wang, Min Zhang, Zihao Kong, Dijia Pan, Ying Chen, Shurui Li, Liang Yuan, Jan D. Reinhardt, Xiao Lu, Yu Zheng

Erschienen in: Basic Research in Cardiology | Ausgabe 1/2023

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Abstract

The successful use of exosomes in therapy after myocardial infarction depends on an improved understanding of their role in cardiac signaling and regulation. Here, we report that exosomes circulating after myocardial infarction (MI) carry LncRNA TUG1 which downregulates angiogenesis by disablement of the HIF-1α/VEGF-α axis and that this effect can be counterbalanced by remote ischemic conditioning (RIC). Rats with MI induced through left coronary artery ligation without (MI model) and with reperfusion (ischemia/reperfusion I/R model) were randomized to RIC, or MI (I/R) or sham-operated (SO) control. Data from one cohort study and one randomized-controlled trial of humans with MI were also utilized, the former involving patients who had not received percutaneous coronary intervention (PCI) and the latter patients with PCI. Exosome concentrations did not differ between intervention groups (RIC vs. control) in rats (MI and I/R model) as well as humans (with and without PCI). However, MI and I/R exosomes attenuated HIF-1α, VEGF-α, and endothelial function. LncRNA TUG1 was increased in MI and I/R exosomes, but decreased in SO and RIC exosomes. HIF-1α expression was downregulated with MI and I/R exosomes but increased with RIC exosomes. Exosome inhibition suppressed HIF-1α upregulation through RIC exosomes. VEGF-α was identified as HIF-1α-regulated target gene. Knockdown of HIF-1α decreased VEGF-α, endothelial cell capability, and tube formation. Overexpression of HIF-1α exerted opposite effects. Transfection and co-transfection of 293 T cells with exosome-inhibitor GW4869 and HIF-1α inhibitor si-HIF-1α confirmed the exosomal-LncRNA TUG1/HIF-1α/VEGF-α pathway. LncRNA TUG1 is a potential therapeutic target after MI with or without reperfusion through PCI.

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Titel: Anti-angiogenic effect of exo-LncRNA TUG1 in myocardial infarction and modulation by remote ischemic conditioning
verfasst von: Yini Dang
Wenjie Hua
Xintong Zhang
Hao Sun
Yingjie Zhang
Binbin Yu
Shengrui Wang
Min Zhang
Zihao Kong
Dijia Pan
Ying Chen
Shurui Li
Liang Yuan
Jan D. Reinhardt
Xiao Lu
Yu Zheng
Publikationsdatum: 01.12.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology / Ausgabe 1/2023
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-022-00975-y

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Anti-angiogenic effect of exo-LncRNA TUG1 in myocardial infarction and modulation by remote ischemic conditioning

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