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The foam cell-derived exosomal miRNA Novel-3 drives neuroinflammation and ferroptosis during ischemic stroke

Qin, Chuan, Dong, Ming-Hao, Tang, Yue, Chu, Yun-Hui, Zhou, Luo-Qi, Zhang, Hang, Yang, Sheng, Zhang, Lu-Yang, Pang, Xiao-Wei, Zhu, Li-Fang, Wang, Wei, Tian, Dai-Shi·2024·Nature Aging
DOI 10.1038/s43587-024-00727-8
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Abstract

Large artery atherosclerosis (LAA) is a prevalent cause of acute ischemic stroke (AIS). Understanding the mechanisms linking atherosclerosis to stroke is essential for developing appropriate intervention strategies. Here, we found that the exosomal miRNA Novel-3 is selectively upregulated in the plasma of patients with LAA-AIS. Notably, Novel-3 was predominantly expressed in macrophage-derived foam cells, and its expression correlated with atherosclerotic plaque vulnerability in patients undergoing carotid endarterectomy. Exploring the function of Novel-3 in a mouse model of cerebral ischemia, we found that Novel-3 exacerbated ischemic injury and targeted microglia and macrophages expressing ionized calcium-binding adapter molecule 1 in peri-infarct regions. Mechanistically, Novel-3 increased ferroptosis and neuroinflammation by interacting with striatin (STRN) and downregulating the phosphoinositide 3-kinase-AKT-mechanistic target of rapamycin signaling pathway. Blocking Novel-3 activity or overexpressing STRN provided neuroprotection under ischemic conditions. Our findings suggest that exosomal Novel-3, which is primarily derived from macrophage-derived foam cells, targets microglia and macrophages in the brain to induce neuroinflammation and could serve as a potential therapeutic target for patients with stroke who have atherosclerosis.

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Research works printed but not linked: 37

  1. Feigin, V. L. et al. World Stroke Organization (WSO): Global Stroke Fact Sheet 2022. Int. J. Stroke 17, 18–29 (2022). · DOI
  2. Malhotra, K., Gornbein, J. & Saver, J. L. Ischemic strokes due to large-vessel occlusions contribute disproportionately to stroke-related dependence and death: a review. Front. Neurol. 8, 651 (2017). · DOI
  3. Wang, Q. et al. A novel perspective on ischemic stroke: a review of exosome and noncoding RNA studies. Brain Sci. https://doi.org/10.3390/brainsci12081000 (2022). · DOI
  4. Wang, C., Li, Z., Liu, Y. & Yuan, L. Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets. Theranostics 11, 3996–4010 (2021). · DOI
  5. Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654–659 (2007). · DOI · Paper page
  6. Kalani, M. Y. S. et al. Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes. J. Extracell. Vesicles 9, 1713540 (2020). · DOI
  7. De Smaele, E., Ferretti, E. & Gulino, A. MicroRNAs as biomarkers for CNS cancer and other disorders. Brain Res. 1338, 100–111 (2010). · DOI
  8. Yang, K., Xiao, Q., Niu, M., Pan, X. & Zhu, X. Exosomes in atherosclerosis: convergence on macrophages. Int. J. Biol. Sci. 18, 3266–3281 (2022). · DOI
  9. Colombo, M., Raposo, G. & Théry, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 30, 255–289 (2014). · DOI · Paper page
  10. Lovett, J. K., Gallagher, P. J., Hands, L. J., Walton, J. & Rothwell, P. M. Histological correlates of carotid plaque surface morphology on lumen contrast imaging. Circulation 110, 2190–2197 (2004). · DOI
  11. Yi, J., Zhu, J., Wu, J., Thompson, C. B. & Jiang, X. Oncogenic activation of PI3K–AKT–mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc. Natl Acad. Sci. USA 117, 31189–31197 (2020). · DOI
  12. Tanti, G. K., Pandey, P., Shreya, S. & Jain, B. P. Striatin family proteins: the neglected scaffolds. Biochim. Biophys. Acta Mol. Cell Res. 1870, 119430 (2023). · DOI
  13. Zheng, S. et al. 17β-Estradiol upregulates striatin protein levels via Akt pathway in human umbilical vein endothelial cells. PLoS ONE 13, e0202500 (2018). · DOI
  14. Li, S. et al. Identification of circular RNA hsa_circ_0001599 as a novel biomarker for large-artery atherosclerotic stroke. DNA Cell Biol. 40, 457–468 (2021). · DOI
  15. Xiao, Q. et al. Comprehensive analysis of peripheral exosomal circRNAs in large artery atherosclerotic stroke. Front. Cell Dev. Biol. 9, 685741 (2021). · DOI
  16. Xiao, Q. et al. Circulating exosomal circRNAs contribute to potential diagnostic value of large artery atherosclerotic stroke. Front. Immunol. 12, 830018 (2021). · DOI
  17. Tang, Y. et al. Exosomal miR-27b-3p secreted by visceral adipocytes contributes to endothelial inflammation and atherogenesis. Cell Rep. 42, 111948 (2023). · DOI
  18. Zhang, Z. G., Buller, B. & Chopp, M. Exosomes—beyond stem cells for restorative therapy in stroke and neurological injury. Nat. Rev. Neurol. 15, 193–203 (2019). · DOI · Paper page
  19. Tenchov, R. et al. Exosomes—nature’s lipid nanoparticles, a rising star in drug delivery and diagnostics. ACS Nano 16, 17802–17846 (2022). · DOI
  20. Alim, I. et al. Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke. Cell 177, 1262–1279 (2019). · DOI
  21. Jiao, L. et al. Iron metabolism mediates microglia susceptibility in ferroptosis. Front. Cell. Neurosci. 16, 995084 (2022). · DOI
  22. Cui, Y. et al. ACSL4 exacerbates ischemic stroke by promoting ferroptosis-induced brain injury and neuroinflammation. Brain Behav. Immun. 93, 312–321 (2021). · DOI
  23. Huang, Y. et al. UBIAD1 alleviates ferroptotic neuronal death by enhancing antioxidative capacity by cooperatively restoring impaired mitochondria and Golgi apparatus upon cerebral ischemic/reperfusion insult. Cell Biosci. 12, 42 (2022). · DOI
  24. Ryan, S. K. et al. Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration. Nat. Neurosci. 26, 12–26 (2023). · DOI
  25. Kapralov, A. A. et al. Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death. Nat. Chem. Biol. 16, 278–290 (2020). · DOI
  26. Absinta, M. et al. A lymphocyte–microglia–astrocyte axis in chronic active multiple sclerosis. Nature 597, 709–714 (2021). · DOI · Paper page
  27. Tang, D., Chen, X., Kang, R. & Kroemer, G. Ferroptosis: molecular mechanisms and health implications. Cell Res. 31, 107–125 (2021). · DOI
  28. Garza, A. E. et al. Striatin heterozygous mice are more sensitive to aldosterone-induced injury. J. Endocrinol. 245, 439–450 (2020). · DOI
  29. Chen, K., Xue, R., Geng, Y. & Zhang, S. Galangin inhibited ferroptosis through activation of the PI3K/AKT pathway in vitro and in vivo. FASEB J. 36, e22569 (2022). · DOI
  30. Konoshenko, M. Y., Lekchnov, E. A., Vlassov, A. V. & Laktionov, P. P. Isolation of extracellular vesicles: general methodologies and latest trends. Biomed Res. Int. 2018, 8545347 (2018). · DOI
  31. Meng, Y. et al. Direct isolation of small extracellular vesicles from human blood using viscoelastic microfluidics. Sci. Adv. 9, eadi5296 (2023). · DOI
  32. Toledano, H., D’Alterio, C., Loza-Coll, M. & Jones, D. L. Dual fluorescence detection of protein and RNA in Drosophila tissues. Nat. Protoc. 7, 1808–1817 (2012). · DOI
  33. Zhou, S. et al. Dandelion polysaccharides ameliorate high-fat-diet-induced atherosclerosis in mice through antioxidant and anti-inflammatory capabilities. Nutrients https://doi.org/10.3390/nu15194120 (2023). · DOI
  34. Li, C.-Y. et al. Inhibition of mTOR pathway restrains astrocyte proliferation, migration and production of inflammatory mediators after oxygen–glucose deprivation and reoxygenation. Neurochem. Int. 83–84, 9–18 (2015). · DOI
  35. Cheng, M. et al. Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells. Nat. Commun. 10, 959 (2019). · DOI
  36. Zhang, Z. et al. The novel estrogenic receptor GPR30 alleviates ischemic injury by inhibiting TLR4-mediated microglial inflammation. J. Neuroinflammation 15, 206 (2018). · DOI
  37. Jia, J. et al. CD11c+ microglia promote white matter repair after ischemic stroke. Cell Death Dis. 14, 156 (2023). · DOI · Paper page

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Metadata

Authors
Qin, C., Dong, M.-H., Tang, Y., Chu, Y.-H., Zhou, L.-Q., Zhang, H., Yang, S., Zhang, L.-Y., Pang, X.-W., Zhu, L.-F., Wang, W., & Tian, D.-S.
ORCID
Venue
Nature Aging
Publisher
Springer Science and Business Media LLC
Published
2024-10-28
Volume
4
Issue
12
Pages
1845-1861
ISSN
2662-8465
DOI
10.1038/s43587-024-00727-8
Cited by
38
References
2
Language
en
Licence
Funders
  • Ministry of Science and Technology of the People's Republic of China (2022ZD0204700)
  • National Natural Science Foundation of China (82271341, 82371404, 81873743)

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