Relation between the plasma levels of LDL-cholesterol and the expression of the early marker of inflammation long pentraxin PTX3 and the stress response gene p66ShcA in pacemaker-implanted patients.
ABSTRACT Our goal was to set up a pilot study to explore the possible relation between the expression of p66((ShcA)) and PTX3, two emerging regulators of stress response and inflammation processes, respectively, and the circulating levels of LDL-cholesterol (LDL), a factor implicated in the development of inflammation and oxidative-stress associated diseases such as atherosclerosis. p66((ShcA)) and PTX3 mRNA contents were determined locally, in subcutaneous adipose specimens of non-diabetic pacemaker-implanted patients, and systemically in the circulating white blood cells (WBC) obtained from the same patients. The mean of the circulating LDL levels (125 mg/dl) was chosen as a threshold to identify two groups here considered to have high (>125 mg/dl) and low (<125 mg/dl) LDL plasma levels. Our data show that PTX3 and p66((ShcA)) mRNA levels are significantly more elevated in WBCs and in adipose tissue samples of patients with high levels of LDL compared to those with low levels. Additionally, a multiple regression analysis indicates that among LDL, TG, HDL, total cholesterol, CRP, creatinine and glucose levels, the only variable significantly affecting p66((ShcA)) and PTX3 mRNA expressions either in adipose tissue or in WBCs is represented by the circulating amount of LDL. In conclusion, our results suggest a potential link between the level of LDL and the expression of two genes involved in inflammation/oxidative stress pathways, i.e., p66((ShcA)) and PTX3, thus contributing to further understand the mechanism through which LDL may mediate the pathogenesis of inflammation and oxidative-stress associated diseases such as atherosclerosis.
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ABSTRACT: Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, is secreted by vascular cells in response to injury, possibly aiming at tuning arterial activation associated with vascular damage. Severe hypercholesterolemia as in familial hypercholesterolemia (FH) promotes vascular inflammation and atherosclerosis; low-density lipoprotein (LDL) apheresis is currently the treatment of choice to reduce plasma lipids in FH. HELP LDL apheresis affects pro- and antiinflammatory biomarkers, however its effects on PTX3 levels are unknown. We assessed the impact of FH and of LDL removal by HELP apheresis on PTX3.PLoS ONE 07/2014; 9(7):e101290. DOI:10.1371/journal.pone.0101290 · 3.53 Impact Factor
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ABSTRACT: Increased oxidative stress and reduced nitric oxide (NO) bioavailability play a causal role in endothelial cell dysfunction occurring in the vasculature of diabetic patients. In this review, we summarized the molecular mechanisms underpinning diabetic endothelial and vascular dysfunction. In particular, we focused our attention on the complex interplay existing among NO, reactive oxygen species (ROS), and one crucial regulator of intracellular ROS production, p66(Shc) protein.03/2014; 2014:193095. DOI:10.1155/2014/193095
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ABSTRACT: Hypercholesterolemia leads to a prothrombotic phenotype. Platelet hyperactivity associated with hypercholesterolemia has been attributed, in part, to oxidative stress. P66Shc is a well-known determinant of cellular and organismal oxidative stress. However, its role in platelet biology is not known. We hypothesized that p66Shc mediates platelet hyperactivation and hyperaggregation in hypercholesterolemia.Biochemical and Biophysical Research Communications 05/2014; DOI:10.1016/j.bbrc.2014.05.029 · 2.28 Impact Factor