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

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.

Correlation of computed tomography with carotid plaque transcriptomes associates calcification with lesion-stabilization

“…We and others [16,17] recently confirmed that molecular pathways related to calcification dominate in end-stage carotid plaques. While osteolytic processes, suggesting reduced calcification, were prevalent in plaques from symptomatic patients, plaques from patients on statin therapy and asymptomatic ones were enriched in processes associated with increased calcification [8].…”

Genetics of Smoking and Risk of Atherosclerotic Cardiovascular Diseases: A Mendelian Randomization Study

“…4 While the mechanism behind the stronger relationship between smoking and PAD is not clear, structural and functional differences within the vascular beds and the complex interplay between smoking and other ASCVD risk factors may contribute. 33,34 The genetic liability to smoking is also associated with cardiometabolic traits that are themselves risk factors ASCVD. The MR finding that increasing genetic liability to smoking is associated with type 2 diabetes is consistent with recent observational and MR studies.…”

Balloon Angioplasty of Infrapopliteal Arteries: A Systematic Review and Proposed Algorithm for Optimal Endovascular Therapy

“…37 Although the actual role of platelets and other cellular elements is still unclear, relatively recent evidence suggests that coagulation factors (ie, thrombosis) might play a more significant role in arterial occlusion and atherothrombosis formation than previously thought. 48,49 Although the differential phenotype of atherosclerotic lesions in different vascular beds is still debatable, 50,51 pathology studies have provided evidence that the composition of atherosclerotic plaques differs significantly between the various locations of PAD, [52][53][54] with vessel calcification being directly correlated to the overall severity of PAD. 55,56 The variability in calcification severity and atherosclerosis degree among the different vascular beds has been attributed to the discrete biomechanical stress conditions of each territory 50,57,58 and to exposure to several cardiovascular risk factors.…”