sodium azide in commercially available c reactive protein preparations does not influence matrix metalloproteinase 2 synthesis and release in cultured human aortic vascular smooth muscle cells

Detection of circulating concentrations of the acute-phase reactant C-reactive protein (CRP), which is synthesized in response to proinflammatory cytokines, is a relevant tool for identifying the involvement of low-grade inflammation in atherosclerosis and for predicting future atherothrombotic events (1). Whether CRP is only a marker or is also an active player in atherosclerotic injury is a matter of intense debate (2). CRP is present in atherosclerotic lesions (3) and can contribute directly to atherothrombosis (4). In particular, CRP induces expression of proatherogenetic molecules in endothelial cells and promotes LDL uptake by macrophages (4). We recently observed that CRP increases synthesis and secretion of matrix metalloproteinase 2 (MMP-2) from cultured human vascular smooth muscle cells (hVSMCs) (5), a mechanism potentially involved in plaque destabilization. Recently, however, the reliability of results concerning CRP obtained in vitro has been

HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: The renal insufficiency and cardiovascular events (RIACE) Italian Multicenter Study

OBJECTIVE: To examine the association of hemoglobin (Hb) A1c variability with microvascular complications in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. RESEARCH DESIGN AND METHODS: Serial (3-5) HbA1c values collected in a 2-year period before enrollment were available from 8,260 subjects from 9 centers (of 15,773 patients from 19 centers). HbA1c variability was measured as the intraindividual SD of 4.52 \ub1 0.76 values. Diabetic retinopathy (DR) was assessed by dilated funduscopy. Chronic kidney disease (CKD) was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. RESULTS: Median and interquartile range of average HbA1c (HbA1c-MEAN) and HbA1c-SD were 7.57% (6.86-8.38) and 0.46% (0.29-0.74), respectively. The highest prevalence of microalbuminuria, macroalbuminuria, reduced eGFR, albuminuric CKD phenotypes, and advanced DR was observed when both HbA1c parameters were above the median and the lowest when both were below the median. Logistic regression analyses showed that HbA1c-SD adds to HbA1c-MEAN as an independent correlate of microalbuminuria and stages 1-2 CKD and is an independent predictor of macroalbuminuria, reduced eGFR, and stages 3-5 albuminuric CKD, whereas HbA1c-MEAN is not. The opposite was found for DR, whereas neither HbA1c-MEAN nor HbA1c-SD affected nonalbuminuric CKD. CONCLUSIONS: In patients with type 2 diabetes, HbA1c variability affects (albuminuric) CKD more than average HbA1c, whereas only the latter parameter affects DR, thus suggesting a variable effect of these measures on microvascular complications