Skip to main content
Top
Published in: Cardiovascular Toxicology 6/2022

01-06-2022

Exosomes Derived from Senescent Endothelial Cells Contain Distinct Pro-angiogenic miRNAs and Proteins

Authors: Shadi Abdolrahman Shaban, Jafar Rezaie, Vahid Nejati

Published in: Cardiovascular Toxicology | Issue 6/2022

Login to get access

Abstract

Exosomes from senescence cells play pivotal roles in endothelium dysfunction. We investigated the exosomal angiogenic cargo of endothelial cells (ECs) in a model of senescence in vitro. After inducing aging by H2O2, the expression of P53, P21, and P16 was investigated by western blotting, while the expression of FMR1, miR-21, and miR-126 were measured by real-time PCR (q-PCR). Oil Red O dye was used to stain cells. Acetylcholinesterase (AChE) assay, transmission electron microscopy (TEM), and western blotting characterized Exosomes. Exosomal miR-21, miR-126, matrix metallopeptidase-9 (MMP-9), and tumor necrosis factor- ɑ (TNF-ɑ) proteins were measured by Q-PCR and western blotting. A wound-healing assay was used to explore the effect of exosomes on ECs migration rate. The results showed that the expression of P53, P21, P16, FMR1, and miR-21 was increased in treated cells as compared with control cells (P < 0.05). In addition, the expression of miR-126 was decreased in treated cells (P < 0.05). The number of Oil Red O-positive-treated cells increased (P < 0.05). The AChE activity of exosomes from treated cells was increased (P < 0.05). In comparison with control cells, an increase in the expression levels of exosomal miR-21 and TNF-ɑ of treated cells coincided with a decrease in the expression levels of miR-126 and MMP-9 levels (P < 0.05). We found that the migration rate of ECs co-cultured with exosomes from treated cells was decreased (P < 0.05). The data indicate ECs under H2O2 condition produce exosomes with distinct cargo that may be useful as a biomarker of age-related vascular disease.
Literature
1.
go back to reference Suzman, R., Beard, J. R., Boerma, T., & Chatterji, S. (2015). Health in an ageing world—What do we know? The Lancet, 385(9967), 484–486.CrossRef Suzman, R., Beard, J. R., Boerma, T., & Chatterji, S. (2015). Health in an ageing world—What do we know? The Lancet, 385(9967), 484–486.CrossRef
2.
go back to reference Di Micco, R., Krizhanovsky, V., Baker, D., & di Fagagna, F. A. (2021). Cellular senescence in ageing: From mechanisms to therapeutic opportunities. Nature Reviews Molecular Cell Biology, 22(2), 75–95.CrossRef Di Micco, R., Krizhanovsky, V., Baker, D., & di Fagagna, F. A. (2021). Cellular senescence in ageing: From mechanisms to therapeutic opportunities. Nature Reviews Molecular Cell Biology, 22(2), 75–95.CrossRef
3.
go back to reference Urbanelli, L., Buratta, S., Sagini, K., Tancini, B., & Emiliani, C. (2016). Extracellular vesicles as new players in cellular senescence. International Journal of Molecular Sciences, 17(9), 1408.CrossRef Urbanelli, L., Buratta, S., Sagini, K., Tancini, B., & Emiliani, C. (2016). Extracellular vesicles as new players in cellular senescence. International Journal of Molecular Sciences, 17(9), 1408.CrossRef
4.
go back to reference Zhang, Y., Liu, Y., Liu, H., & Tang, W. H. (2019). Exosomes: Biogenesis, biologic function and clinical potential. Cell & Bioscience, 9(1), 1–18.CrossRef Zhang, Y., Liu, Y., Liu, H., & Tang, W. H. (2019). Exosomes: Biogenesis, biologic function and clinical potential. Cell & Bioscience, 9(1), 1–18.CrossRef
5.
go back to reference Rezaie, J., Aslan, C., Ahmadi, M., Zolbanin, N. M., Kashanchi, F., & Jafari, R. (2021). The versatile role of exosomes in human retroviral infections: From immunopathogenesis to clinical application. Cell & Bioscience, 11(1), 1–15.CrossRef Rezaie, J., Aslan, C., Ahmadi, M., Zolbanin, N. M., Kashanchi, F., & Jafari, R. (2021). The versatile role of exosomes in human retroviral infections: From immunopathogenesis to clinical application. Cell & Bioscience, 11(1), 1–15.CrossRef
6.
go back to reference Caporali, A., & Emanueli, C. (2011). MicroRNA regulation in angiogenesis. Vascular pharmacology, 55(4), 79–86.CrossRef Caporali, A., & Emanueli, C. (2011). MicroRNA regulation in angiogenesis. Vascular pharmacology, 55(4), 79–86.CrossRef
7.
go back to reference Jafari, R., Rahbarghazi, R., Ahmadi, M., Hassanpour, M., & Rezaie, J. (2020). Hypoxic exosomes orchestrate tumorigenesis: Molecular mechanisms and therapeutic implications. Journal of Translational Medicine, 18(1), 1–14.CrossRef Jafari, R., Rahbarghazi, R., Ahmadi, M., Hassanpour, M., & Rezaie, J. (2020). Hypoxic exosomes orchestrate tumorigenesis: Molecular mechanisms and therapeutic implications. Journal of Translational Medicine, 18(1), 1–14.CrossRef
8.
go back to reference Voghel, G., Thorin-Trescases, N., Farhat, N., Nguyen, A., Villeneuve, L., Mamarbachi, A. M., Fortier, A., Perrault, L. P., Carrier, M., & Thorin, E. (2007). Cellular senescence in endothelial cells from atherosclerotic patients is accelerated by oxidative stress associated with cardiovascular risk factors. Mechanisms of Ageing and Development, 128(11–12), 662–671.CrossRef Voghel, G., Thorin-Trescases, N., Farhat, N., Nguyen, A., Villeneuve, L., Mamarbachi, A. M., Fortier, A., Perrault, L. P., Carrier, M., & Thorin, E. (2007). Cellular senescence in endothelial cells from atherosclerotic patients is accelerated by oxidative stress associated with cardiovascular risk factors. Mechanisms of Ageing and Development, 128(11–12), 662–671.CrossRef
10.
go back to reference Wong, P.-F., Kind-Leng Tong, J. J., Khor, E.-S., Lai, S.-L., & Mustafa, M. R. (2019). Senescent HUVECs-secreted exosomes trigger endothelial barrier dysfunction in young endothelial cells. EXCLI Journal, 18, 764.PubMedPubMedCentral Wong, P.-F., Kind-Leng Tong, J. J., Khor, E.-S., Lai, S.-L., & Mustafa, M. R. (2019). Senescent HUVECs-secreted exosomes trigger endothelial barrier dysfunction in young endothelial cells. EXCLI Journal, 18, 764.PubMedPubMedCentral
11.
go back to reference Lunyak, V. V., Amaro-Ortiz, A., & Gaur, M. (2017). Mesenchymal stem cells secretory responses: Senescence messaging secretome and immunomodulation perspective. Frontiers in Genetics, 8, 220.CrossRef Lunyak, V. V., Amaro-Ortiz, A., & Gaur, M. (2017). Mesenchymal stem cells secretory responses: Senescence messaging secretome and immunomodulation perspective. Frontiers in Genetics, 8, 220.CrossRef
12.
go back to reference Xu, D., & Tahara, H. (2013). The role of exosomes and microRNAs in senescence and aging. Advanced Drug Delivery Reviews, 65(3), 368–375.CrossRef Xu, D., & Tahara, H. (2013). The role of exosomes and microRNAs in senescence and aging. Advanced Drug Delivery Reviews, 65(3), 368–375.CrossRef
13.
go back to reference Chowdhary, S. (2019). The effects of oxidative stress on inducing senescence in human fibroblasts. Journal of the South Carolina Academy of Science, 16(2), 2. Chowdhary, S. (2019). The effects of oxidative stress on inducing senescence in human fibroblasts. Journal of the South Carolina Academy of Science, 16(2), 2.
14.
go back to reference Rezaie, J., Nejati, V., Khaksar, M., Oryan, A., Aghamohamadzadeh, N., Shariatzadeh, M. A., Rahbarghazi, R., & Mehranjani, M. S. (2018). Diabetic sera disrupted the normal exosome signaling pathway in human mesenchymal stem cells in vitro. Cell and Tissue Research, 374(3), 555–565.CrossRef Rezaie, J., Nejati, V., Khaksar, M., Oryan, A., Aghamohamadzadeh, N., Shariatzadeh, M. A., Rahbarghazi, R., & Mehranjani, M. S. (2018). Diabetic sera disrupted the normal exosome signaling pathway in human mesenchymal stem cells in vitro. Cell and Tissue Research, 374(3), 555–565.CrossRef
15.
go back to reference Jabbari, N., Nawaz, M., & Rezaie, J. (2019). Ionizing radiation increases the activity of exosomal secretory pathway in MCF-7 human breast cancer cells: A possible way to communicate resistance against radiotherapy. International Journal of Molecular Sciences, 20(15), 3649.CrossRef Jabbari, N., Nawaz, M., & Rezaie, J. (2019). Ionizing radiation increases the activity of exosomal secretory pathway in MCF-7 human breast cancer cells: A possible way to communicate resistance against radiotherapy. International Journal of Molecular Sciences, 20(15), 3649.CrossRef
17.
go back to reference Feghhi, M., Rezaie, J., Akbari, A., Jabbari, N., Jafari, H., Seidi, F., & Szafert, S. (2021). Effect of multi-functional polyhydroxylated polyhedral oligomeric silsesquioxane (POSS) nanoparticles on the angiogenesis and exosome biogenesis in human umbilical vein endothelial cells (HUVECs). Materials & Design, 197, 109227.CrossRef Feghhi, M., Rezaie, J., Akbari, A., Jabbari, N., Jafari, H., Seidi, F., & Szafert, S. (2021). Effect of multi-functional polyhydroxylated polyhedral oligomeric silsesquioxane (POSS) nanoparticles on the angiogenesis and exosome biogenesis in human umbilical vein endothelial cells (HUVECs). Materials & Design, 197, 109227.CrossRef
18.
go back to reference Kiyoshima, T., Enoki, N., Kobayashi, I., Sakai, T., Nagata, K., Wada, H., Fujiwara, H., Ookuma, Y., & Sakai, H. (2012). Oxidative stress caused by a low concentration of hydrogen peroxide induces senescence-like changes in mouse gingival fibroblasts. International Journal of Molecular Medicine, 30(5), 1007–1012.CrossRef Kiyoshima, T., Enoki, N., Kobayashi, I., Sakai, T., Nagata, K., Wada, H., Fujiwara, H., Ookuma, Y., & Sakai, H. (2012). Oxidative stress caused by a low concentration of hydrogen peroxide induces senescence-like changes in mouse gingival fibroblasts. International Journal of Molecular Medicine, 30(5), 1007–1012.CrossRef
19.
go back to reference Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., Gargiulo, G., Testa, G., Cacciatore, F., Bonaduce, D., & Abete, P. (2018). Oxidative stress, aging, and diseases. Clinical Interventions in Aging, 13, 757.CrossRef Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., Gargiulo, G., Testa, G., Cacciatore, F., Bonaduce, D., & Abete, P. (2018). Oxidative stress, aging, and diseases. Clinical Interventions in Aging, 13, 757.CrossRef
20.
go back to reference Yao, H. R., Liu, J., Plumeri, D., Cao, Y. B., He, T., Lin, L., Li, Y., Jiang, Y. Y., Li, J., & Shang, J. (2011). Lipotoxicity in HepG2 cells triggered by free fatty acids. American Journal of Translational Research, 3(3), 284.PubMedPubMedCentral Yao, H. R., Liu, J., Plumeri, D., Cao, Y. B., He, T., Lin, L., Li, Y., Jiang, Y. Y., Li, J., & Shang, J. (2011). Lipotoxicity in HepG2 cells triggered by free fatty acids. American Journal of Translational Research, 3(3), 284.PubMedPubMedCentral
21.
go back to reference Lujambio, A. (2016). To clear, or not to clear (senescent cells)? That is the question. BioEssays, 38, S56–S64.CrossRef Lujambio, A. (2016). To clear, or not to clear (senescent cells)? That is the question. BioEssays, 38, S56–S64.CrossRef
22.
go back to reference Althubiti, M., Lezina, L., Carrera, S., Jukes-Jones, R., Giblett, S. M., Antonov, A., Barlev, N., Saldanha, G. S., Pritchard, C. A., Cain, K., & Macip, S. (2014). Characterization of novel markers of senescence and their prognostic potential in cancer. Cell Death & Disease, 5(11), e1528–e1528.CrossRef Althubiti, M., Lezina, L., Carrera, S., Jukes-Jones, R., Giblett, S. M., Antonov, A., Barlev, N., Saldanha, G. S., Pritchard, C. A., Cain, K., & Macip, S. (2014). Characterization of novel markers of senescence and their prognostic potential in cancer. Cell Death & Disease, 5(11), e1528–e1528.CrossRef
23.
go back to reference Macip, S., Igarashi, M., Berggren, P., Yu, J., Lee, S. W., & Aaronson, S. A. (2003). Influence of induced reactive oxygen species in p53-mediated cell fate decisions. Molecular and Cellular Biology, 23(23), 8576–8585.CrossRef Macip, S., Igarashi, M., Berggren, P., Yu, J., Lee, S. W., & Aaronson, S. A. (2003). Influence of induced reactive oxygen species in p53-mediated cell fate decisions. Molecular and Cellular Biology, 23(23), 8576–8585.CrossRef
24.
go back to reference Chiaradia, E., Tancini, B., Emiliani, C., Delo, F., Pellegrino, R. M., Tognoloni, A., Urbanelli, L., & Buratta, S. (2021). Extracellular vesicles under oxidative stress conditions: Biological properties and physiological roles. Cells, 10(7), 1763.CrossRef Chiaradia, E., Tancini, B., Emiliani, C., Delo, F., Pellegrino, R. M., Tognoloni, A., Urbanelli, L., & Buratta, S. (2021). Extracellular vesicles under oxidative stress conditions: Biological properties and physiological roles. Cells, 10(7), 1763.CrossRef
25.
go back to reference Soraya, H., Sani, N. A., Jabbari, N., & Rezaie, J. (2021). Metformin increases exosome biogenesis and secretion in U87 MG human glioblastoma cells: A possible mechanism of therapeutic resistance. Archives of Medical Research, 52(2), 151–162.CrossRef Soraya, H., Sani, N. A., Jabbari, N., & Rezaie, J. (2021). Metformin increases exosome biogenesis and secretion in U87 MG human glioblastoma cells: A possible mechanism of therapeutic resistance. Archives of Medical Research, 52(2), 151–162.CrossRef
26.
go back to reference Lespagnol, A., Duflaut, D., Beekman, C., Blanc, L., Fiucci, G., Marine, J. C., Vidal, M., Amson, R., & Telerman, A. (2008). Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice. Cell Death and Differentiation, 15(11), 1723.CrossRef Lespagnol, A., Duflaut, D., Beekman, C., Blanc, L., Fiucci, G., Marine, J. C., Vidal, M., Amson, R., & Telerman, A. (2008). Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice. Cell Death and Differentiation, 15(11), 1723.CrossRef
27.
go back to reference Cheng, Y., Liu, X., Zhang, S., Lin, Y., Yang, J., & Zhang, C. (2009). MicroRNA-21 protects against the H2O2-induced injury on cardiac myocytes via its target gene PDCD4. Journal of Molecular and Cellular Cardiology, 47(1), 5–14.CrossRef Cheng, Y., Liu, X., Zhang, S., Lin, Y., Yang, J., & Zhang, C. (2009). MicroRNA-21 protects against the H2O2-induced injury on cardiac myocytes via its target gene PDCD4. Journal of Molecular and Cellular Cardiology, 47(1), 5–14.CrossRef
28.
go back to reference Talepoor, A. G., Kalani, M., Dahaghani, A. S., & Doroudchi, M. (2017). Hydrogen peroxide and lipopolysaccharide differentially affect the expression of microRNAs 10a, 33a, 21, 221 in endothelial cells before and after coculture with monocytes. International Journal of Toxicology, 36(2), 133–141.CrossRef Talepoor, A. G., Kalani, M., Dahaghani, A. S., & Doroudchi, M. (2017). Hydrogen peroxide and lipopolysaccharide differentially affect the expression of microRNAs 10a, 33a, 21, 221 in endothelial cells before and after coculture with monocytes. International Journal of Toxicology, 36(2), 133–141.CrossRef
29.
go back to reference Alique, M., Bodega, G., Giannarelli, C., Carracedo, J., & Ramírez, R. (2019). MicroRNA-126 regulates Hypoxia-Inducible Factor-1α which inhibited migration, proliferation, and angiogenesis in replicative endothelial senescence. Scientific Reports, 9(1), 1–19.CrossRef Alique, M., Bodega, G., Giannarelli, C., Carracedo, J., & Ramírez, R. (2019). MicroRNA-126 regulates Hypoxia-Inducible Factor-1α which inhibited migration, proliferation, and angiogenesis in replicative endothelial senescence. Scientific Reports, 9(1), 1–19.CrossRef
30.
go back to reference Zhou, J., Wang, K. C., Wu, W., Subramaniam, S., Shyy, J. Y. J., Chiu, J. J., Li, J. Y. S., & Chien, S. (2011). MicroRNA-21 targets peroxisome proliferators-activated receptor-α in an autoregulatory loop to modulate flow-induced endothelial inflammation. Proceedings of the National Academy of Sciences, 108(25), 10355–10360.CrossRef Zhou, J., Wang, K. C., Wu, W., Subramaniam, S., Shyy, J. Y. J., Chiu, J. J., Li, J. Y. S., & Chien, S. (2011). MicroRNA-21 targets peroxisome proliferators-activated receptor-α in an autoregulatory loop to modulate flow-induced endothelial inflammation. Proceedings of the National Academy of Sciences, 108(25), 10355–10360.CrossRef
31.
go back to reference Dellago, H., Preschitz‐Kammerhofer, B., Terlecki‐Zaniewicz, L., Schreiner, C., Fortschegger, K., Chang, M. W. F., Hackl, M., Monteforte, R., Kuhnel, H., Schosserer, M., Gruber, F., Tschachler, E., Scheideler, M., Grillari-Voglauer, R., Grillari, J., & Wieser, M. (2013). High levels of oncomi R-21 contribute to the senescence-induced growth arrest in normal human cells and its knock-down increases the replicative lifespan. Aging Cell, 12(3), 446–458.CrossRef Dellago, H., Preschitz‐Kammerhofer, B., Terlecki‐Zaniewicz, L., Schreiner, C., Fortschegger, K., Chang, M. W. F., Hackl, M., Monteforte, R., Kuhnel, H., Schosserer, M., Gruber, F., Tschachler, E., Scheideler, M., Grillari-Voglauer, R., Grillari, J., & Wieser, M. (2013). High levels of oncomi R-21 contribute to the senescence-induced growth arrest in normal human cells and its knock-down increases the replicative lifespan. Aging Cell, 12(3), 446–458.CrossRef
32.
go back to reference Freedman, J. E., Gerstein, M., Mick, E., Rozowsky, J., Levy, D., Kitchen, R., Das, S., Shah, V., Danielson, K., Beaulieu, L., Navarro, F. C. P. Wang, Y., Galeev, T. R., Holman, A., Kwong, R. Y., Murthy, V., Tanriverdi, S. E., Koupenova, M., Mikhalev, E., & Tanriverdi, K. (2016). Diverse human extracellular RNAs are widely detected in human plasma. Nature Communications, 7(1), 1–14. Freedman, J. E., Gerstein, M., Mick, E., Rozowsky, J., Levy, D., Kitchen, R., Das, S., Shah, V., Danielson, K., Beaulieu, L., Navarro, F. C. P. Wang, Y., Galeev, T. R., Holman, A., Kwong, R. Y., Murthy, V., Tanriverdi, S. E., Koupenova, M., Mikhalev, E., & Tanriverdi, K. (2016). Diverse human extracellular RNAs are widely detected in human plasma. Nature Communications, 7(1), 1–14.
33.
go back to reference Fish, J. E., Santoro, M. M., Morton, S. U., Yu, S., Yeh, R. F., Wythe, J. D., Lvey, K. N., Bruneau, B. J., Stainier, D. Y. R., & Srivastava, D. (2008). miR-126 regulates angiogenic signaling and vascular integrity. Developmental Cell, 15(2), 272–284.CrossRef Fish, J. E., Santoro, M. M., Morton, S. U., Yu, S., Yeh, R. F., Wythe, J. D., Lvey, K. N., Bruneau, B. J., Stainier, D. Y. R., & Srivastava, D. (2008). miR-126 regulates angiogenic signaling and vascular integrity. Developmental Cell, 15(2), 272–284.CrossRef
34.
go back to reference Wozniak, A. L., Adams, A., King, K. E., Dunn, W., Christenson, L. K., Hung, W.-T., & Weinman, S. A. (2020). The RNA binding protein FMR1 controls selective exosomal miRNA cargo loading during inflammation. Journal of Cell Biology, 219(10), e201912074.CrossRef Wozniak, A. L., Adams, A., King, K. E., Dunn, W., Christenson, L. K., Hung, W.-T., & Weinman, S. A. (2020). The RNA binding protein FMR1 controls selective exosomal miRNA cargo loading during inflammation. Journal of Cell Biology, 219(10), e201912074.CrossRef
35.
go back to reference Lee, B.-R., Kim, J.-H., Choi, E.-S., Cho, J.-H., & Kim, E. (2018). Effect of young exosomes injected in aged mice. International Journal of Nanomedicine, 13, 5335.CrossRef Lee, B.-R., Kim, J.-H., Choi, E.-S., Cho, J.-H., & Kim, E. (2018). Effect of young exosomes injected in aged mice. International Journal of Nanomedicine, 13, 5335.CrossRef
37.
go back to reference Yabluchanskiy, A., Ma, Y., Iyer, R. P., Hall, M. E., & Lindsey, M. L. (2013). Matrix metalloproteinase-9: Many shades of function in cardiovascular disease. Physiology, 28(6), 391–403.CrossRef Yabluchanskiy, A., Ma, Y., Iyer, R. P., Hall, M. E., & Lindsey, M. L. (2013). Matrix metalloproteinase-9: Many shades of function in cardiovascular disease. Physiology, 28(6), 391–403.CrossRef
38.
go back to reference Wang, Y., Xu, J., Zhang, X., Wang, C., Huang, Y., Dai, K., & Zhang, X. (2017). TNF-α-induced LRG1 promotes angiogenesis and mesenchymal stem cell migration in the subchondral bone during osteoarthritis. Cell Death & Disease, 8(3), e2715–e2715.CrossRef Wang, Y., Xu, J., Zhang, X., Wang, C., Huang, Y., Dai, K., & Zhang, X. (2017). TNF-α-induced LRG1 promotes angiogenesis and mesenchymal stem cell migration in the subchondral bone during osteoarthritis. Cell Death & Disease, 8(3), e2715–e2715.CrossRef
39.
go back to reference Chen, C. Y., Rao, S. S., Ren, L., Hu, X. K., Tan, Y. J., Hu, Y., Luo, J., Liu, Y.-W., Yin, H., Huang, J., Cao, J., Wang, Z.-X., Liu, Z.-Z., Liu, H.-M., Tang, S.-Y., Xu, R., & Xie, H. (2018). Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics, 8(6), 1607.CrossRef Chen, C. Y., Rao, S. S., Ren, L., Hu, X. K., Tan, Y. J., Hu, Y., Luo, J., Liu, Y.-W., Yin, H., Huang, J., Cao, J., Wang, Z.-X., Liu, Z.-Z., Liu, H.-M., Tang, S.-Y., Xu, R., & Xie, H. (2018). Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics, 8(6), 1607.CrossRef
40.
go back to reference Shakeri, H., Gevaert, A. B., Schrijvers, D. M., De Meyer, G. R., De Keulenaer, G. W., Guns, P. J. D., Lemmens., K., & Segers, V. F. (2018). Neuregulin-1 attenuates stress-induced vascular senescence. Cardiovascular Research, 114(7), 1041–1051.CrossRef Shakeri, H., Gevaert, A. B., Schrijvers, D. M., De Meyer, G. R., De Keulenaer, G. W., Guns, P. J. D., Lemmens., K., & Segers, V. F. (2018). Neuregulin-1 attenuates stress-induced vascular senescence. Cardiovascular Research, 114(7), 1041–1051.CrossRef
41.
go back to reference Tonini, T., Rossi, F., & Claudio, P. P. (2003). Molecular basis of angiogenesis and cancer. Oncogene, 22(42), 6549–6556.CrossRef Tonini, T., Rossi, F., & Claudio, P. P. (2003). Molecular basis of angiogenesis and cancer. Oncogene, 22(42), 6549–6556.CrossRef
42.
go back to reference Sun, L., Zhu, W., Zhao, P., Zhang, J., Lu, Y., Zhu, Y., Zhao, W., Liu, Y., Chen, Q., & Zhang, F. (2020). Down-regulated exosomal MicroRNA-221–3p derived from senescent mesenchymal stem cells impairs heart repair. Frontiers in Cell and Developmental Biology, 8, 263.CrossRef Sun, L., Zhu, W., Zhao, P., Zhang, J., Lu, Y., Zhu, Y., Zhao, W., Liu, Y., Chen, Q., & Zhang, F. (2020). Down-regulated exosomal MicroRNA-221–3p derived from senescent mesenchymal stem cells impairs heart repair. Frontiers in Cell and Developmental Biology, 8, 263.CrossRef
Metadata
Title
Exosomes Derived from Senescent Endothelial Cells Contain Distinct Pro-angiogenic miRNAs and Proteins
Authors
Shadi Abdolrahman Shaban
Jafar Rezaie
Vahid Nejati
Publication date
01-06-2022
Publisher
Springer US
Published in
Cardiovascular Toxicology / Issue 6/2022
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-022-09740-y

Other articles of this Issue 6/2022

Cardiovascular Toxicology 6/2022 Go to the issue