Myeloid IκBα Deficiency Promotes Atherogenesis by Enhancing Leukocyte Recruitment to the Plaques

Activation of the transcription factor NF-κB appears to be involved in different stages of atherogenesis. In this paper we investigate the role of NF-κB inhibitor IκBα in atherosclerosis. Myeloid-specific deletion of IκBα results in larger and more advanced lesions in LDL-R-deficient mice without affecting the compositional phenotype of the plaques or systemic inflammatory markers in the plasma. We show that IκBα-deleted macrophages display enhanced adhesion to an in vitro endothelial cell layer, coinciding with an increased expression of the chemokine CCL5. Also, in vivo we found that IκBαdel mice had more leukocytes adhering to the luminal side of the endothelial cell layers that cover the atherosclerotic plaques. Moreover, we introduce ER-MP58 in this paper as a new immunohistochemical tool for quantifying newly recruited myeloid cells in the atherosclerotic lesion. This staining confirms that in IκBαdel mice more leukocytes are attracted to the plaques. In conclusion, we show that IκBα deletion in myeloid cells promotes atherogenesis, probably through an induced leukocyte recruitment to plaques

Pulse wave velocity in children following renal transplantation

Background. Arterial stiffness (ASt) increases with age, a process accelerated by uraemia and reversed by transplantation (Tx). Increased ASt results in an elevated pulse wave velocity (PWV). Methods. To compare the PWV of Tx patients (n = 25, age = 15.1/95% CI = 13.5-16.7/year) and healthy controls, three control groups were formed: matched for age (A), for height and weight (H/W) and for age and height (A/H), respectively. To avoid bias from the growth deficit of Tx, firstly Z-scores of PWV were calculated (PWV-Z). Second, the PWV/height (PWV/h) ratio was assessed. Pre-Tx serum Ca, P, PTH and the cumulative dose of calcitriol (cCTL) were also analysed. Finally, Tx patients were compared to ESRD patients (n = 11). PWV was measured by applanation tonometry. Results. Tx were smaller than A and older than H/W. The PWV of Tx differed only from H/W and A/H. PWV-Z and PWV/h of Tx were increased compared to all control groups. They correlated with the CaxP and cCTL before Tx and were independent of age. Patients with creatinine clearance > 90 ml/min/1.73 m(2) or < 1 year on dialysis had lower PWV-Z and PWV/h than ESRD. Conclusion. Controls that matched for both age and height should be used to assess PWV in children with growth failure. PWV-Z is a universal age-independent parameter of PWV in cases of growth retardation; PWV/h is a simple alternative of PWV-Z. CaxP and cCTL are major determinants of ASt after Tx. PWV may be reduced after Tx suggesting that the uraemia-induced cardiovascular changes might be reversible