Treatment with sulphated galactan inhibits macrophage chemotaxis and reduces intraplaque macrophage content in atherosclerotic mice.

Experimental data from animal models and clinical studies support connections between the haemostasis and inflammation in atherogenesis. These interfaces among inflammation and thrombogenesis have been suggested as targets for pharmacological intervention to reduce disease progression. We hypothesize that the recently discovered antithrombotic drug Sulphated Galactan (SG) (isolated from the red marine alga Acanthophora muscoides) might reduce atherosclerotic plaque vulnerability and inflammatory gene expression in 10-week aged apolipoprotein E deficient (ApoE-/-) mice under high-cholesterol diet for additional 11weeks. Then, the underlying cellular mechanisms were investigated in vitro. SG (10mg/kg) or Vehicle was subcutaneously injected from week 6 until week 11 of the diet. Treatment with SG reduced intraplaque macrophage and Tissue Factor (TF) content as compared to Vehicle-treated animals. Intraplaque TF co-localized and positively correlated with macrophage rich-areas. No changes on atherosclerotic plaque size, and other intraplaque features of vulnerability (such as lipid, neutrophil, MMP-9 and collagen contents) were observed. Moreover, mRNA expression of MMPs, chemokines and genetic markers of Th1/2/reg/17 lymphocyte polarization within mouse aortic arches and spleens was not affected by SG treatment. In vitro, treatment with SG dose-dependently reduced macrophage chemotaxis without affecting TF production. Overall, the chronic SG treatment was well tolerated. In conclusion, our results indicate that SG treatment reduced intraplaque macrophage content (by impacting on cell recruitment) and, concomitantly, intraplaque TF content of potential macrophage origin in atherosclerotic mice.

Serum resistin and inflammatory and endothelial activation markers in obese adolescents.

OBJECTIVES: To assess the level of serum resistin in obese and lean children and to establish a relationship with circulating inflammatory and vascular markers. STUDY DESIGN: This is a cross-sectional study including 67 obese and 62 lean children (mean age 10.9 ± 2.8 years, age range 5.4-16.6 years). We assessed circulating hormones (insulin, leptin, insulin-like growth factor 1), markers of inflammation (resistin, high sensitivity C-reactive protein, interleukin-6, chemokine ligand 2), and endothelial cell activation (vascular and intercellular adhesion molecules: vascular cell adhesion molecule 1 and intercellular adhesion molecule; E-selectin; P-selectin; endothelin 1). RESULTS: Body weight, body mass index (BMI), insulin, leptin, high-sensitivity C-reactive protein, vascular adhesion molecule 1, and E-selectin levels were significantly higher in obese than in lean subjects. Resistin was similar among the groups in the prepubertal period, but increased significantly in the obese adolescents (18.6 ± 24.9) compared with lean subjects (7.9 ± 10.7 ng/mL; P = .038). Resistin was not associated with BMI z score (P > .05). Subjects with resistin levels above 9 (ng/mL) had higher concentration of interleukin-6, chemokine ligand 2, endothelin-1, and insulin-like growth factor 1 but not of leptin, insulin, or BMI. CONCLUSION: Resistin was increased in obese adolescents independently of the quantity of the adipose tissue. In this population, increased resistin levels were related to inflammation and endothelial activation. We may hypothesize that interventions aiming to diminish resistin expression may slow down atherogenesis in adolescents.