Biomedical subjects

Giovanni Davi

Publications and source records attributed to Giovanni Davi.

3 recordsLinked to original sources

PubMed2003

Enhanced interleukin-1beta in hypercholesterolemia: effects of simvastatin and low-dose aspirin.

BACKGROUND: This study was aimed at verifying whether activation of platelets might represent a source of interleukin (IL)-1beta levels in hypercholesterolemia. To this purpose, we compared the effects of a short-term treatment with simvastatin or low-dose aspirin on circulating levels of this cytokine. METHODS AND RESULTS: Fifty patients with hypercholesterolemia were randomly allocated to receive an 8-week therapeutic course of simvastatin 20 mg daily (n=25) or aspirin 100 mg daily (n=25). Baseline soluble (s) P-selectin directly correlated with IL-1beta (P<0.0001) and C-reactive protein (CRP) (P<0.05) but not with von Willebrand factor, total cholesterol, or LDL cholesterol levels. Furthermore, sP-selectin (P<0.02) and IL-1beta (P<0.0001) levels were independently related to CRP by multiple regression analysis. Both drugs were associated with comparable, significant reductions in IL-1beta and sP-selectin. Simvastatin, but not aspirin treatment, significantly lowered CRP levels (P<0.05). The change in IL-1beta levels correlated with the change in sP-selectin in patients randomized to either simvastatin (Rho, 0.42; P<0.05) or aspirin (Rho, 0.42; P<0.05). In contrast, the simvastatin-induced change in IL-1beta did not correlate with the change in CRP levels. CONCLUSIONS: This study suggests that platelets might contribute to IL-1beta production in hypercholesterolemia, thus providing an additional link between inflammation and the prothrombotic state in this setting.

Adult↗

PubMed2003

Physical exercise increases urinary excretion of lipoxin A4 and related compounds.

Lipoxins (LX) are lipoxygenase-derived eicosanoids with potent anti-inflammatory activities and vascular bed-dependent vasodilatory actions. LX can be formed in vitro and in vivo in a number of conditions, and we have reported that immunoreactive LXA(4) (iLXA(4)) is physiologically excreted with human urine. Using a recently developed LX extraction method coupled to an ELISA, we examined whether iLXA(4) excretion was modified by strenuous exercise, which is known to trigger potential LX-forming events. Maximal exertion significantly increased iLXA(4) urinary excretion in nine healthy volunteers (0.061 +/- 0.023 vs. 0.113 +/- 0.057 ng/mg creatinine; P = 0.028). iLXA(4) levels returned to baseline after 6 h and increased, although at a smaller extent, after 24 h. A significant correlation (r = 0.988) was denoted between iLXA(4) ELISA measurements and reversed-phase high-performance liquid chromatography quantitation of a previously described urinary tetraene, confirming its LXA(4)-related nature. These findings show for the first time that an increase in excretion of LXA(4)-related compounds can be observed in response to strenuous exercise. This may be the reflection of an enhanced LX biosynthesis, which may represent a safeguard mechanism that keeps the inflammatory reaction triggered by physical stress under control.

Adult↗

PubMed2003

Platelet activation, inflammatory mediators and hypercholesterolemia.

Atherogenic cofactors, such as altered cholesterol metabolism, may impact locally on inflammatory responses in atherosclerotic lesions. Blood levels of inflammatory markers (e.g., C-reactive protein, fibrinogen) have been associated with hypercholesterolemia and with overt atherothrombotic disorders. More recently. cytokines (e.g., interleukin-6, interleukin-1beta) and soluble adhesion molecules (e.g., selectins, intercellular adhesion molecule-1, vascular cell adhesion molecule-1) have been associated with both hypercholesterolemia and atherosclerotic disease, suggesting their use as potential therapeutic targets for the non-specific "anti-inflammatory" treatment of atherosclerosis. The inflammatory response associated with hypercholesterolemia involves not only the intrinsic cells of the artery wall. but also circulating cells. Platelets participate in this disease process through the release of a wide variety of biologically active substances. An imbalance of the hemostatic system and persistent in vivo platelet activation can be observed in hypercholesterolemia and may have pathophysiological implications in the development and progression of atherosclerotic plaques. Recent findings on the inflammatory actions of platelets have established the potential for a previously unrecognized biologic role for platelets in inflammation and vascular injury, and have opened new perspectives in the comprehension of the pathogenetic mechanism(s) of atherosclerosis. Stimulated platelets actively synthesize proinflammatory cytokines (e.g., CD40L, IL-1beta) and are able to release chemokines (i.e., platelet factor-4, RANTES) which have been all involved in the inflammatory process associated with hypercholesterolemia. This review will summarize the present understanding of the interplay between hypercholesterolemia, inflammation and platelet activation in the development and progression of atherosclerosis, and we also discuss the effects of lipid-lowering treatment on these phenomena.

Animals↗