Association between Expression of Insulin-like Growth Factor-1 (IGF-1), IGF-1 Receptor (IGF-1R), and Hypertension-Mediated Organ Damage (HMOD) Parameters in Leukocytes and Plasma of Children/Adolescents with Primary Hypertension.

A decrease in IGF-1 is often linked to inflammation. Low systemic and local IGF-1 production and downregulation of IGF-1R expression may precede and predict PH development in children/adolescents. Leukocyte mRNA expression of IGF-1 and its receptor (IGF-1R) and plasma IGF-1 were measured in a group of 39 PH children/adolescents (29 boys and 10 girls) and 35 age-matched normotensive children (19 boys and 16 girls) using the RT-PCR and ELISA tests. The expression of the IGF-1R protein was assessed by flow cytometry. Plasma IGF-1 concentration was evaluated with ELISA. The expression of IGF-1 and IGF-1R and plasma concentrations of IGF-1 did not differ between groups. However, the PH children had a decreased percentage in IGF-1R-bearing lymphocytes (p = 0.02) and monocytes (p = 0.0003), as well as a low density of IGF-R in monocytes (p = 0.02). The IGF-1 expression was negatively correlated with pulse-wave velocity (PWV) (r = -0.49), systolic blood pressure (SBP) (-0.44), and carotid intima-media thickness (cIMT) (-0.43). The IGF-1R expression was negatively correlated with PWV (r = -0.42) and SBP (r = -0.41). Our results suggest that early subclinical hypertensive arterial injury is associated with lower activity of IGF-1-IGF-1R expression and loss of protective actions.

Implications of the Matrix Metalloproteinases, Their Tissue Inhibitors and Some Other Inflammatory Mediators Expression Levels in Children Obesity-Related Phenotypes.

OBJECTIVES: Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endo-peptidases engaged in many biological processes including adipogenesis, angiogenesis, and tissue remodeling. Fat tissue infiltration by peripheral leukocytes plays an important role in transition of fat tissue residual, non-inflammatory status into the pro-inflammatory one, resulting in fat tissue inflammation and expansion as well as production of many mediators like adipokines and cytokines. The aim of this study was to investigate the expression of MMPs, their endogenous tissue inhibitors (TIMPs), and selected inflammatory mediators in leukocytes and plasma of children with simple obesity to find their associations with obesity-related phenotypes. MATERIAL AND METHODS: Twenty-six overweight/obese children and twenty-three healthy volunteers participated in the study. The leukocyte mRNA expression levels of MMP-2, -9, -12 -14, TIMP-1, -2, and IL-6 were analyzed by the real time quantitative PCR. Plasma MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios as well as the concentrations of MMP-9, TIMP-1, IL-1 beta, IL-6, TNF- alpha, leptin and resistin were tested by ELISA assays. Gelatin zymography was used to assess the activity of the leukocyte MMPs proteins. RESULTS: The obese children showed the following: a) increased expression of leukocyte TIMP-1 and slight elevation (close to statistical significance) of leukocyte MMP-9 (p = 0.054), the decline in MMP-2, b) elevation of plasma MMP-9, leptin, and MMP9/TIMP1 ratio, c) reduced expression of plasma TNF-alpha and MMP-2/TIMP-2 ratio. Several negative correlations were found: TIMP2 vs. ALT (r = -0.536), AST (r = -0.645) and TTG (r = -0.438), IL-6 vs. GGTP (r = -0.815), and MMP12 vs. TTG (r = -0.488), leptin vs. ALT (r = -0.569), MMP-9 vs. total cholesterol (r = -0.556). The only positive correlation was that of plasma leptin level vs. GGTP (r = 0.964). CONCLUSIONS: At the beginning of obesity development (children), possibly compensatory reactions prevail, reflected here by an increase in the expression of leukocyte MMPs inhibitor TIMP-1, decrease in the level of leukocyte MMP-2 and plasma MMP-2, MMP2/TIMP-2 ratio, low plasma TNF-alpha and negative correlations between the expression of TIMP-2 and liver (AST, ALT) or fat (TTG) inflammatory markers.

Postoperative kinetics of pentraxin 3 (PTX3) after congenital heart surgery with cardiopulmonary bypass in pediatric patients.

BACKGROUND: Pentraxins are inflammatory proteins and markers of acute-phase responses. They are divided into short and long subgroups based on the length of the N-terminal region. The most studied short pentraxin is the C-reactive protein (CRP), which is known to be expressed in various inflammatory conditions, including surgical procedures. On the other hand, much less is known about the kinetics of long pentraxin 3 (PTX3) in surgical patients, especially in the pediatric population. The aim of this prospective study was to determine the early postoperative kinetics of PTX3 in relation to procalcitonin (PCT) and CRP levels in children undergoing congenital heart surgery with cardiopulmonary bypass (CPB). METHODS: A total of 21 children (9 boys and 12 girls, mean age 12 months) were included in the study. Blood samples for determination of CRP, PCT, and PTX3 levels were collected before the surgery and then immediately after its completion (postoperative day 0, POD 0) and subsequently at POD 1, 2, and 3. RESULTS: Serum PTX3 concentrations increased significantly between POD 0 and POD 1 (mean values were 12.2 and 72.4 ng/ml, respectively, p<0.001), decreased between POD 1 and POD 2 (mean values were 72.4 and 23.6 ng/ml, respectively, p<0.001), and normalized on POD 3 (the mean value was 1.2 ng/ml). CONCLUSIONS: PTX3 concentrations are markedly elevated during the first postoperative day. Under normal circumstances, PTX3 rises and falls quickly, and its second rise in the early postoperative period may be abnormal, however, further studies are necessary.

Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Peripheral Blood Leukocytes and Plasma of Children with Nonalcoholic Fatty Liver Disease.

Gene expression profiles of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) were evaluated in peripheral blood leukocytes of children with nonalcoholic fatty liver disease (NAFLD). Gene expression patterns were correlated with their plasma protein counterparts, systemic parameters of liver injury, and selected markers of inflammation. The MMP-2, MMP-9, MMP-12, MMP-14, TIMP-1, TIMP-2, TGF-ß, and IL-6 transcripts levels were tested by the real-time PCR. Plasma concentrations of MMP-9, TIMP-1, MMP-9/TIMP-1 ratio, MMP-2/TIMP-2 ratio, sCD14, leptin, resistin, IL-1 beta, and IL-6 and serum markers of liver injury were estimated by ELISA. The MMP-9, TIMP-2 expression levels, plasma amounts of MMP-9, TIMP-1, and the MMP-9/TIMP-1 ratio were increased in children with NAFLD. Concentrations of AST, ALT, GGT, and leptin were elevated in serum patients with NAFLD, while concentration of other inflammatory or liver injury markers was unchanged. The MMP-2 and MMP-9 levels correlated with serum liver injury parameters (ALT and GGT concentrations, respectively); there were no other correlations between MMP/TIMP gene expression profiles, their plasma counterparts, and serum inflammatory markers. Association of MMP-2 and MMP-9 expression with serum liver injury parameters (ALT, GGT) may suggest leukocyte engagement in the early stages of NAFLD development which possibly precedes subsequent systemic inflammatory responses.