Potential of dapagliflozin to prevent vascular remodeling in the rat carotid artery following balloon injury.

Autor: Matsushita K; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France; Université de Strasbourg, Pôle D'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France., Sato C; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France; Université de Strasbourg, Pôle D'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France., Bruckert C; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France., Gong D; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France., Amissi S; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France., Hmadeh S; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France., Fakih W; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France., Remila L; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France., Lessinger JM; CHU de Strasbourg, Laboratoire de Biochimie Clinique et Biologie Moléculaire, 67091, Strasbourg, France., Auger C; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France., Jesel L; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France; Université de Strasbourg, Pôle D'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France., Ohlmann P; Université de Strasbourg, Pôle D'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France., Kauffenstein G; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France., Schini-Kerth VB; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France., Morel O; UR 3074, Translational CardioVascular Medicine, Biomedicine Research Centre of Strasbourg, FMTS, Université de Strasbourg, Strasbourg, France; Université de Strasbourg, Pôle D'Activité Médico-Chirurgicale Cardio-Vasculaire, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France; Hanoï Medical University, Hanoi, Viet Nam. Electronic address: olivier.morel@chru-strasbourg.fr.
Jazyk: angličtina
Zdroj: Atherosclerosis [Atherosclerosis] 2024 Oct; Vol. 397, pp. 117595. Date of Electronic Publication: 2024 May 23.
DOI: 10.1016/j.atherosclerosis.2024.117595
Abstrakt: Background and Aims: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of cardiovascular events independently of glycemic control. However, the possibility that SGLT2 inhibitors improve vascular restenosis is unknown. The aim of this study was to examine whether dapagliflozin could prevent neointima thickening following balloon injury and, if so, to determine the underlying mechanisms.
Methods: Saline, dapagliflozin (1.5 mg/kg/day), or losartan (30 mg/kg/day) was administered orally for five weeks to male Wistar rats. Balloon injury of the left carotid artery was performed a week after starting the treatment and rats were sacrificed 4 weeks later. The extent of neointima was assessed by histomorphometric and immunofluorescence staining analyses. Vascular reactivity was assessed on injured and non-injured carotid artery rings, changes of target factors by immunofluorescence, RT-qPCR, and histochemistry.
Results: Dapagliflozin and losartan treatments reduced neointima thickening by 32 % and 27 %, respectively. Blunted contractile responses to phenylephrine and relaxations to acetylcholine and down-regulation of eNOS were observed in the injured arteries. RT-qPCR investigations indicated an increased in gene expression of inflammatory (IL-1beta, VCAM-1), oxidative (p47phox, p22phox) and fibrotic (TGF-beta1) markers in the injured carotid. While these changes were not affected by dapagliflozin, increased levels of AT1R and NTPDase1 (CD39) and decreased levels of ENPP1 were observed in the restenotic carotid artery of the dapagliflozin group.
Conclusions: Dapagliflozin effectively reduced neointimal thickening. The present data suggest that dapagliflozin prevents restenosis through interfering with angiotensin and/or extracellular nucleotides signaling. SGLT2 represents potential new target for limiting vascular restenosis.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE