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Article Dans Une Revue Scientific Reports Année : 2018

Identification of genomic differences among peripheral arterial beds in atherosclerotic and healthy arteries

Marie-Françoise Heymann
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Résumé

Calcification is independently associated with cardiovascular events and morbidity. The calcification burden in atherosclerotic lesions quantitatively and qualitatively differs between arterial beds. Cardiovascular risk factors (CVRF) differentially affect plaque development between arterial beds. The aim of this study was to evaluate the impact of CVRF on atherosclerotic plaque calcification and to further study the molecular arterial heterogeneity that could account for these differences. Histological analysis was performed on atherosclerotic plaques from 153 carotid, 97 femoral and 28 infrapopliteal arteries. CVRF showed minor associations with plaque calcification: age and hypertension affected only the overall presence of calcification but not the type of the calcification, which significantly differed between arterial beds. Transcriptome analysis revealed distinct gene expression profiles associated with each territory in atherosclerotic and healthy arteries. Canonical pathway analysis showed the preferential involvement of immune system-related processes in both atherosclerotic and healthy carotid arteries. Bone development-related genes were among those mostly enriched in atherosclerotic and healthy femoral arteries, which are more prone to developing endochondral calcification. This study highlights the heterogeneous nature of arteries from different peripheral vascular beds and contributes to a better understanding of atherosclerosis formation and evolution. Vascular calcification is an independent predicting factor for cardiovascular events and morbidity 1. Vascular calcification is associated with a worse prognosis after lower limb artery endovascular revascularization: multi-variate analysis reported that the percentage of calcified plaque is an independent predictor of binary restenosis at 12 months 2. Vascular calcification favors plaque rupture and contributes to hypertension depending on its localization and extent. Anatomo-histological studies have shown that atherosclerotic plaque compositions largely differ between anatomical locations in peripheral arterial diseases (PAD). Plaque calcifications are heterogeneous with various types of calcifications, including predominantly microcalcifications in carotid arteries (CA) and bone tissue (osteoid metaplasia) in femoral arteries (FA) 3,4. These differences do not derive from distinct stages of plaque progression , as femoral plaques tend to develop later than those in CA 5. The discrepancies in calcification burden could therefore derive from different shear stress conditions 6 , intrinsic biological differences between vascular cells as suggested by their diverse embryological origins 7,8 , or exposure to different cardiovascular risk factors (CVRF), as CVRF also differentially affect plaque development differentially between arterial beds 9–12 .
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Dates et versions

inserm-01725150 , version 1 (07-03-2018)

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Marja Steenman, Olivier Espetia, Blandine Maurel, Béatrice Guyomarch, Marie-Françoise Heymann, et al.. Identification of genomic differences among peripheral arterial beds in atherosclerotic and healthy arteries. Scientific Reports, 2018, 8 (1), pp.3940. ⟨10.1038/s41598-018-22292-y⟩. ⟨inserm-01725150⟩
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