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Aims: Inflammation is a key regulatory process that links hypercholesterolemia and immune mechanisms promoting atherosclerosis. Inflammatory biomarkers may be helpful to better define the atherosclerotic burden in patients with high cholesterol levels such as familial hypercholesterolemia (FH). Our aim was to evaluate the concentration of S100A12 protein in FH patients and its association with pulse wave velocity (PWV). Methods: We measured glucose and lipid profile, S100A12, sRAGE, esRAGE and PWV in 39 patients with a genetically confirmed diagnosis of FH and 39 hypercholesterolemic subjects without a clinical diagnosis of FH (Dutch score ≤ 3). All subjects were on statin treatment at the time of the enrollment. Results: No difference of glucose and lipid profile was found in the two groups. FH patients had higher S100A12 plasma levels than non-FH subjects (12.87 ± 4.82 vs. 8.57 ± 4.87 ng/mL, p < 0.01). No difference of hs-CRP, sRAGE and esRAGE was found between the two groups. Also, PWV was higher in FH patients than non-FH subjects (8.63 ± 0.92 vs. 6.68 ± 0.73 m/s, p < 0.05). Finally, S100A12 was independently correlated with age (p < 0.01), genetic mutation (p < 0.01) and PWV (p < 0.001). Conclusions: FH patients exhibited higher S100A12 levels than non-FH subjects. A novel vascular inflammation pathway, other than hs-CRP, might be useful to better characterize cardiovascular risk profile. [ABSTRACT FROM AUTHOR]

Aims: The dyslipidemia associated with type 2 diabetes is a major risk factor for the development of atherosclerosis. Trans-intestinal cholesterol excretion (TICE) has recently been shown to contribute, together with the classical hepatobiliary route, to fecal cholesterol excretion and cholesterol homeostasis. The aim of this study was to develop an in vitro cell model to investigate enterocyte-related processes of TICE. Methods: Differentiated Caco-2/TC7 cells were grown on transwells and incubated basolaterally (blood side) with human plasma and apically (luminal side) with lipid micelles. Radioactive and fluorescent cholesterol tracers were used to investigate cholesterol uptake at the basolateral membrane, intracellular distribution and apical excretion. Results: Our results show that cholesterol is taken up at the basolateral membrane, accumulates intracellularly as lipid droplets and undergoes a cholesterol acceptor-facilitated and progressive excretion through the apical membrane of enterocytes. The overall process is abolished at 4 °C, suggesting a biologically active phenomenon. Moreover, this trans-enterocytic retrograde cholesterol transport displays some TICE features like modulation by PCSK9 and an ABCB1 inhibitor. Finally, we highlight the involvement of microtubules in the transport of plasma cholesterol from basolateral to apical pole of enterocytes. Conclusions: The human Caco-2/TC7 cell line appears a good in vitro model to investigate the enterocytic molecular mechanisms of TICE, which may help to identify intestinal molecular targets to enhance reverse cholesterol transport and fight against dyslipidemia. [ABSTRACT FROM AUTHOR]