Increased levels of endothelial microparticles CD144 (VE-Cadherin) positives in type 2 diabetic patients with coronary noncalcified plaques evaluated by multidetector computed tomography (MDCT).

OBJECTIVE: The combination of both morphological and cellular markers of subclinical atherosclerosis, in addition to conventional risk factors, may help to improve cardiovascular prevention in type 2 diabetic patients. The aim of our cross-sectional study was to evidence a putative increase in endothelial (EMP) or platelet (PMP) microparticles, in type 2 diabetic patients with coronary noncalcified plaques detected by multidetector CT (MDCT). METHODS AND RESULTS: Microparticles and coronary MDCT were assessed in 56 type 2 diabetic patients with different cardiovascular risk levels. Both EMP (r=0.35, p=0.022) and PMP (rho=0.34, p=0.022) were correlated with hsCRP. EMP were elevated in patients with acute coronary syndromes (p=0.034). EMP count was significantly higher in the presence of noncalcified diseased segments (p=0.01). By contrast, there was no association between hsCRP and noncalcified atheroma. This increase in EMP in noncalcified diseased segment carriers remained borderline significant after adjustment for coronary heart disease and hsCRP. Conversely, there was no association of PMP count with noncalcified diseased segments and no difference in PMP count between patients with and without acute coronary syndrome. No significant association between either EMP and PMP counts and mixed or calcified diseased segments was observed. CONCLUSIONS: We report for the first time an association between plasma EMP-CD144+ and coronary noncalcified plaques assessed by MDCT in a population of type 2 diabetic patients. EMP might be used as a surrogate marker of unstable plaques, and might help to improve cardiovascular prediction in diabetic patients with intermediate risk.

CCAAT/enhancer-binding proteins (C/EBPs) regulate the basal and cAMP-induced transcription of the human 11beta-hydroxysteroid dehydrogenase encoding gene in adipose cells.

Android obesity is often associated with a metabolic syndrome characterized, in particular, by a type 2 diabetes and cardiovascular problems. This could be induced by an excess of local production of glucocorticoids (GC) by adipose tissue (or other tissues). This production of GC by its target tissues depends on the 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) enzyme. Our aim was to characterize some mechanisms which control the expression of the human 11betaHSD1 gene (hHSD11B1) in preadipocytes. By using different luciferase constructs containing fragments of the hHSD11B1 promoter, we demonstrate that two members of the CCAAT/enhancer-binding protein family, C/EBPalpha and C/EBPbeta, are required for the basal transcriptional activity of HSD11B1 in 3T3-L1 preadipocyte cells. This effect depends on the binding of each isoform to specific binding sites. Mutation of either one of these sites induced a 40-50% decrease of the constitutive activity of the hHSD11B1 promoter. A forskolin treatment of 3T3-L1 preadipocyte cells induced an increased endogenous expression of HSD11B1. By transfection studies using the hHSD11B1 luciferase constructs, it appears that C/EBPbeta was strongly involved in this induction, as the forskolin stimulation was suppressed after mutation of the C/EBPbeta binding site. Part of the mechanism involved the increase of nuclear C/EBPbeta protein levels induced by forskolin and a phosphorylation step associated with an enhanced binding of the transcription factor to its site. These data indicate that members of the C/EBP family control intracellular levels of GC in preadipocytes via the regulation of the constitutive and cAMP-dependent expressions of HSD11B1.