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JACC Basic Transl Sci. 2019 Feb 25;4(1):72-82. doi: 10.1016/j.jacbts.2018.10.006. eCollection 2019 Feb.

miR-29b Mediates the Chronic Inflammatory Response in Radiotherapy-Induced Vascular Disease.

Author information

1
Cardiovascular Medicine Unit, Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden.
2
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
3
Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
4
INSERM UMR_S1116, Université de Lorraine, Vandoeuvre-lès-Nancy, France.
5
Technical University Munich, Department of Vascular and Endovascular Surgery, Munich, Germany.
6
German Center for Cardiovascular Research (DZHK) partner site Munich, Munich, Germany.
7
University of Caen Normandie, LARIA-CIMAP, Caen, France.
8
Department of Reconstructive Plastic Surgery, Karolinska University Hospital, Stockholm, Sweden.

Abstract

As a consequence of the success of present-day cancer treatment, radiotherapy-induced vascular disease is emerging. This disease is caused by chronic inflammatory activation and is likely orchestrated in part by microRNAs. In irradiated versus nonirradiated conduit arteries from patients receiving microvascular free tissue transfer reconstructions, irradiation resulted in down-regulation of miR-29b and up-regulation of miR-146b. miR-29b affected inflammation and adverse wound healing through its targets pentraxin-3 and dipeptidyl-peptidase 4. In vitro and in vivo, we showed that miR-29b overexpression therapy, through inhibition of pentraxin-3 and dipeptidyl-peptidase 4, could dampen the vascular inflammatory response.

KEYWORDS:

Apoe–/–, apolipoprotein E knockout; DIG, digoxigenin; DPP4, Dpp4, dipeptidyl-peptidase 4; FFT, free flap tissue transfer; HCtAEC, human carotid artery endothelial cell; HCtASMC, human carotid artery smooth muscle cell; NR, nonirradiated; PTX3, Ptx3, pentraxin-3; RNA, ribonucleic acid; SMC, smooth muscle cell; TGF, tumor growth factor; arteriosclerosis; inflammation; mRNA, messenger ribonucleic acid; miRNA, microRNA; microRNA; radiotherapy; vRTx, radiation vasculopathy

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