Lower endothelial progenitor cell number, family history of cardiovascular disease and reduced HDL-cholesterol levels are associated with shorter leukocyte telomere length in healthy young adults.

BACKGROUND AND AIMS: Leukocyte telomere length (LTL) is a novel marker of cardiovascular (CV) risk. The aim of the study was to investigate the major determinants of LTL in a healthy young population at very low CV risk. METHODS AND RESULTS: LTL was determined in 82 healthy subjects (49M/33F; age37 ± 9yrs), normotensive and not taking any medication with different family history of cardiovascular disease (CVD) (24yes/58no). Fasting blood samples were drawn in all subjects for the determination of lipid profile, high sensitive C-reactive protein, uric acid, Plasminogen Activator Inhibitor-1 (PAI-1), LTL and Endothelial Progenitor Cell (EPC) number. LTL was assessed with a specific real-time PCR reaction in leukocyte DNA samples. LTL resulted inversely correlated with family history of CVD (t = 2.70; p = 0.009), age (r = -0.238; p = 0.032), waist circumference (r = -0.256; p = 0.02), triglycerides (r = -0.218; p = 0.049), PAI-1 (r = -0.288; p = 0.009) and directly correlated with HDL-cholesterol (r = 0.316; p = 0.004) and EPC number (r = 0.358; p = 0.002). At a multivariate analysis, family history of CVD (p = 0.013), EPC count (p = 0.003), and HDL-cholesterol (p = 0.017) were independently associated with LTL (r = 0.62). CONCLUSION: LTL is independently associated to CV risk factors also in healthy young adults.

Macrophage polarization: the answer to the diet/inflammation conundrum?

Macrophages, a heterogeneous and ubiquitous cell population representing up to 15% of the cellular content of different types of tissue, are the principal cell mediators in response to pathogens, inflammation process, tissue homeostasis and repair and play a pivotal role in atherosclerosis and insulin resistance because of their capacity to be the major source of inflammatory cytokines, which can function through paracrine and endocrine mechanisms. Recently, differently activated macrophage populations have been described, depending on a large variety of microenvironmental signals, and it is now recognized that their activation plays a crucial role in the development and progression of atherosclerosis. There is good evidence of the ability of conjugated linoleic acids and polyphenolic compounds to modulate inflammation in experimental models involving macrophages. This observation leaves room to the intriguing hypothesis that macrophage polarization could represent one of the unifying mechanisms through which specific food components can exert anti-inflammatory effects in humans, contributing to the prevention of chronic diseases strongly linked to inflammation, such as atherosclerosis. Future studies should be addressed to substantiate this hypothesis, investigating whether or not physiological concentrations of food-derived metabolites can perturb macrophage activation in vitro. On the in vivo side, the evaluation of macrophage populations in tissues, however complex, should be included among the analyses performed in observational and intervention studies, in order to understand if macrophage activation is involved in the anti-inflammatory activity of a specific dietary regimen.

Reduced circulating endothelial progenitor cell number in healthy young adult hyperinsulinemic men.

BACKGROUND AND AIMS: The number of Endothelial Progenitor Cells (EPCs) is considered a novel marker of cardiovascular (CV) disease. It is not clear which are the main determinants of EPC number in apparently healthy subjects in the absence of overt clinical CV or metabolic abnormalities. We evaluated the main clinical determinants of EPC levels in a population of healthy subjects with normal glucose tolerance. METHODS AND RESULTS: EPC number was determined in 122 healthy subjects (73M/49F;36.6 ± 8yrs). Blood samples were collected to test biochemical variables. OGTT was performed and insulin resistance/compensatory hyperinsulinemia was defined according to fasting plasma insulin (FPI) levels. EPCs were identified as cells co-expressing CD133/CD34/KDR antigens by flow-cytometry. CD133(+)/KDR(+) count inversely correlated with BMI (rho=-0.18;p < 0.05), waist circumference (-0.2;<0.05), diastolic (-0.23;<0.01) and systolic blood pressure (-0.21;<0.05), uric acid (-0.24;<0.005), PAI-1 (-0.197; <0.05) and FPI (-0.2;<0.05) and directly correlated with HDL cholesterol (0.182;<0.05). CD34(+)/CD133(+)/KDR(+) count inversely correlated with uric acid (-0.28;<0.005) and FPI (-0.2;<0.05). EPC number was lower in males (p < 0.05) and gender was the only independent predictor of EPC count (p < 0.05). By dividing the population in four subgroups based on gender and insulin resistance, CD133(+)/KDR(+) levels were lower in insulin resistant compared to insulin sensitive males (p < 0.05) with no differences in females. CONCLUSION: The male gender is an independent predictor of low EPC levels in healthy subjects. This might contribute to explaining the higher CV risk in males compared to pre-menopausal age-matched females. In this study a reduced EPC number seems to be associated with insulin resistance in male subjects.