Differential Proteomic Profiles of Coronary Serum Exosomes in Acute Myocardial Infarction Patients with or Without Diabetes Mellitus: ANGPTL6 Accelerates Regeneration of Endothelial Cells Treated with Rapamycin via MAPK Pathways.

Autor: Wang W; Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, 250014, China., Zhao Y; Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, 250014, China., Zhu P; Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, 250014, China., Jia X; Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, 250014, China., Wang C; Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, 250014, China., Zhang Q; Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, 250014, China., Li H; Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, 250014, China., Wang J; Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, 250014, China. 15964529689@126.com., Hou Y; Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, 250014, China. houyinglong2010@hotmail.com.
Jazyk: angličtina
Zdroj: Cardiovascular drugs and therapy [Cardiovasc Drugs Ther] 2024 Feb; Vol. 38 (1), pp. 13-29. Date of Electronic Publication: 2022 Jul 12.
DOI: 10.1007/s10557-022-07365-5
Abstrakt: Purpose: Delayed re-endothelialization after coronary drug-eluting stent implantation is associated with an increased incidence of late in-stent thrombosis. Serum exosomes exhibit controversial effects on promoting endothelialization. This study aimed to compare the angiogenic effects of serum exosomes derived from patients with acute myocardial infarction (AMI) and AMI plus diabetes mellitus (DM) and to explore the underlying mechanisms.
Methods: Serum exosomes derived from patients in the control (Con-Exos), AMI (AMI-Exos), and AMI plus DM (AMI+DM-Exos) groups were isolated and identified using standard assays. CCK-8, wound healing, and tube formation assays were performed to detect the angiogenic abilities of serum exosomes on rapamycin-conditioned human umbilical vein endothelial cells (HUVECs). Differential proteomic profiles between AMI-Exos and AMI+DM-Exos were analyzed by mass spectrometry. The effects and potential mechanisms of exosomal angiopoietin-like 6 (ANGPTL6) were investigated.
Results: Functional assays indicated that compared with Con-Exos, AMI-Exos enhanced, whereas AMI+DM-Exos inhibited the cell proliferation, migration, and tube formation of rapamycin-conditioned HUVECs. Subsequently, 28 differentially expressed proteins between AMI-Exos and AMI+DM-Exos were identified, which were correlated with material transportation, immunity, and inflammatory reaction. Moreover, ANGPTL6 was highly enriched in AMI-Exos. Overexpression and knockdown of ANGPTL6 enhanced and inhibited angiogenesis, respectively. Furthermore, the effect of ANGPTL6 on angiogenesis was mediated via the activation of ERK 1/2, JNK, and p38 pathways. The inhibition of ERK 1/2 signaling markedly attenuated the migration abilities of overexpressing ANGPTL6.
Conclusion: Diabetes impairs the regenerative capacities of serum exosomes. Exosomal ANGPTL6 contributes to endothelial repair and is a novel therapeutic target for enhanced stent endothelization.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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