Senescence induces miR-409 to down-regulate CCL5 and impairs angiogenesis in endothelial progenitor cells.

Autor: Chou YH; Department of Medicine, MacKay Medical College, New Taipei, Taiwan.; Institute of Biomedical Sciences, MacKay Medical College, New Taipei, Taiwan., Lee YN; Division of Preventive Cardiology & Pulmonary Circulation Medicine, Department of Cardiovascular Medicine, Department of Internal Medicine and Department of Medical Research, MacKay Memorial Hospital, New Taipei, Taiwan., Su CH; Division of Preventive Cardiology & Pulmonary Circulation Medicine, Department of Cardiovascular Medicine, Department of Internal Medicine and Department of Medical Research, MacKay Memorial Hospital, New Taipei, Taiwan., Lee HI; Department of Medicine, MacKay Medical College, New Taipei, Taiwan., Hsieh CL; Division of Preventive Cardiology & Pulmonary Circulation Medicine, Department of Cardiovascular Medicine, Department of Internal Medicine and Department of Medical Research, MacKay Memorial Hospital, New Taipei, Taiwan., Tien TY; Division of Preventive Cardiology & Pulmonary Circulation Medicine, Department of Cardiovascular Medicine, Department of Internal Medicine and Department of Medical Research, MacKay Memorial Hospital, New Taipei, Taiwan., Lin CF; Department of Medicine, MacKay Medical College, New Taipei, Taiwan.; Division of Preventive Cardiology & Pulmonary Circulation Medicine, Department of Cardiovascular Medicine, Department of Internal Medicine and Department of Medical Research, MacKay Memorial Hospital, New Taipei, Taiwan., Yeh HI; Division of Preventive Cardiology & Pulmonary Circulation Medicine, Department of Cardiovascular Medicine, Department of Internal Medicine and Department of Medical Research, MacKay Memorial Hospital, New Taipei, Taiwan., Wu YJ; Department of Medicine, MacKay Medical College, New Taipei, Taiwan.; Institute of Biomedical Sciences, MacKay Medical College, New Taipei, Taiwan.; Division of Preventive Cardiology & Pulmonary Circulation Medicine, Department of Cardiovascular Medicine, Department of Internal Medicine and Department of Medical Research, MacKay Memorial Hospital, New Taipei, Taiwan.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Jun; Vol. 28 (12), pp. e18489.
DOI: 10.1111/jcmm.18489
Abstrakt: This study explores the impact of senescence on autocrine C-C motif chemokine ligand 5 (CCL5) in human endothelial progenitor cell (EPCs), addressing the poorly understood decline in number and function of EPCs during ageing. We examined the effects of replication-induced senescence on CCL5/CCL5 receptor (CCR5) signalling and angiogenic activity of EPCs in vitro and in vivo. We also explored microRNAs controlling CCL5 secretion in senescent EPCs, its impact on EPC angiogenic activity, and validated our findings in humans. CCL5 secretion and CCR5 levels in senescent EPCs were reduced, leading to attenuated angiogenic activity. CCL5 enhanced EPC proliferation via the CCR5/AKT/P70S6K axis and increased vascular endothelial growth factor (VEGF) secretion. Up-regulation of miR-409 in senescent EPCs resulted in decreased CCL5 secretion, inhibiting the angiogenic activity, though these negative effects were counteracted by the addition of CCL5 and VEGF. In a mouse hind limb ischemia model, CCL5 improved the angiogenic activity of senescent EPCs. Analysis involving 62 healthy donors revealed a negative association between CCL5 levels, age and Framingham Risk Score. These findings propose CCL5 as a potential biomarker for detection of EPC senescence and cardiovascular risk assessment, suggesting its therapeutic potential for age-related cardiovascular disorders.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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