Abstract
BackgroundAlthough endothelial cell adhesion molecules (CAMs) are postulated to play a key role in early atherosclerosis, studies on endothelial CAMs are mainly pertained to middle-aged populations and populations with an unfavourable cardiovascular risk burden. Therefore, this study evaluated whether circulating endothelial CAMs are related to cardiovascular magnetic resonance imaging (CMR) derived indicators of arterial wall alterations in a random sample of young adults from the general population.MethodsThis cross-sectional study is part of the general-population-based Atherosclerosis-Monitoring-and-Biomarker-measurements-In-The-YOuNg (AMBITYON) cohort study. In 131 adults (age: 25–35 years), demography, anthropometry and a lipid spectrum was acquired. Thoracic aortic wall area, wall thickness and pulse wave velocity (PWV) were measured using a 3 T CMR-system. From stored blood samples, four CAMs (E-selectin, P-selectin, vascular CAM-1 and intercellular CAM-1) were measured using dedicated methods. Linear mixed-effects regression analysis was used to evaluate the relation of these CAMs with the selected aortic characteristics.ResultsOf the studied endothelial CAMs, P-selectin related to natural logarithm transformed aortic wall thickness (β = 0.18 mm/(μg/ml), [95% confidence interval: 0.04, 0.31], p = 0.01) whereas E-selectin related to natural logarithm transformed aortic PWV (β = 3.01 (m/s)/(μg/ml), [95% confidence interval: 0.08, 5.95], p = 0.04). Of note, VCAM-1 and ICAM-1 did not relate to the selected aortic characteristics.ConclusionsIn young adults from the general population, circulating P-selectin and E-selectin levels appear positively related to CMR-derived aortic wall thickness and PWV, possibly pointing towards atherogenic inflammatory arterial wall alterations inflicted by these CAMs already in young adulthood.Trial registrationNetherlands National Trial Register (NTR): NTR4742, Registered 18 August 2014, retrospectively registered.
Highlights
Endothelial cell adhesion molecules (CAMs) are postulated to play a key role in early atherosclerosis, studies on endothelial CAMs are mainly pertained to middle-aged populations and populations with an unfavourable cardiovascular risk burden
Relation between circulating endothelial biomarkers and aortic characteristics The crude model, Model 1, showed that P-selectin significantly and positively related to both aortic wall area (β = 0.21 cm2 per 1 μg/ml increase [95% confidence intervals (CI): 0.04, 0.38], p = 0.02) and log-aortic wall thickness (β = 0.19 mm per 1 μg/ml increase [95% CI: 0.06, 0.32], p = 0.005)
Model 1 demonstrated a significant, positive relation between E-selectin and log-aortic pulse wave velocity (PWV) (β = 3.83 m/s per 1 μg/ml increase [95% CI: 1.14, 6.53], p = 0.006) (Table 1)
Summary
Endothelial cell adhesion molecules (CAMs) are postulated to play a key role in early atherosclerosis, studies on endothelial CAMs are mainly pertained to middle-aged populations and populations with an unfavourable cardiovascular risk burden. A crucial multi-step biological mechanism that is considered a fundamental early promotor of atherosclerosis is an enhanced homing and adherence of leukocytes to the vascular endothelium and their ensuing migration through the arterial wall into its intima where they instigate the migration of smooth muscle cells (SMCs) and the evolution of foam cells and lipid deposits [3]. The multi-step mechanism is induced by atherogenic stimuli (i.e. lipoproteins, inflammatory cytokines) and mediated by various endothelial cell adhesion molecules (CAMs) that are expressed on the surface of endothelial cells [3,4,5]. Given the early life origins of atherosclerosis, their role in younger, asymptomatic populations warrants exploration
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