Abstract
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.
Highlights
Vascular calcification is an independent predicting factor for cardiovascular events and morbidity[1]
Tobacco use was significantly associated with atherosclerotic femoral arteries (FA); diabetes mellitus was more frequent in patients with diseased infrapopliteal arteries (IPA)
Osteoid metaplasia is very frequent in FA, whereas microcalcifications are more prominent in carotid arteries (CA)
Summary
Vascular calcification is an independent predicting factor for cardiovascular events and morbidity[1]. Vascular calcification favors plaque rupture and contributes to hypertension depending on its localization and extent. 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 CA5. The discrepancies in calcification burden could 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 differentially affect plaque development differentially between arterial beds[9,10,11,12]. The differential impact of systemic CVRF on vascular beds and differential atherosclerotic plaque calcifications and compositions suggest biological arterial heterogeneity. Sulkava et al identified genes differentially expressed between atherosclerotic plaques from CA and FA and from abdominal aortas in humans, reflecting plaque heterogeneity between these beds[25]
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