Francesca Sanna
University of Cagliari
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Francesca Sanna.
Journal of Nutrition | 2009
Barbara Batetta; Mikko Griinari; Gianfranca Carta; Elisabetta Murru; Alessia Ligresti; Lina Cordeddu; Elena Giordano; Francesca Sanna; Tiziana Bisogno; Sabrina Uda; Maria Collu; Inge Bruheim; Vincenzo Di Marzo; Sebastiano Banni
Dietary (n-3) long-chain PUFA [(n-3) LCPUFA] ameliorate several metabolic risk factors for cardiovascular diseases, although the mechanisms of these beneficial effects are not fully understood. In this study, we compared the effects of dietary (n-3) LCPUFA, in the form of either fish oil (FO) or krill oil (KO) balanced for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content, with a control (C) diet containing no EPA and DHA and similar contents of oleic, linoleic, and alpha-linolenic acids, on ectopic fat and inflammation in Zucker rats, a model of obesity and related metabolic dysfunction. Diets were fed for 4 wk. Given the emerging evidence for an association between elevated endocannabinoid concentrations and metabolic syndrome, we also measured tissue endocannabinoid concentrations. In (n-3) LCPUFA-supplemented rats, liver triglycerides and the peritoneal macrophage response to an inflammatory stimulus were significantly lower than in rats fed the control diet, and heart triglycerides were lower, but only in KO-fed rats. These effects were associated with a lower concentration of the endocannabinoids, anandamide and 2-arachidonoylglycerol, in the visceral adipose tissue and of anandamide in the liver and heart, which, in turn, was associated with lower levels of arachidonic acid in membrane phospholipids, but not with higher activity of endocannabinoid-degrading enzymes. Our data suggest that the beneficial effects of a diet enriched with (n-3) LCPUFA are the result of changes in membrane fatty acid composition. The reduction of substrates for inflammatory molecules and endocannabinoids may account for the dampened inflammatory response and the physiological reequilibration of body fat deposition in obese rats.
The FASEB Journal | 2003
Barbara Batetta; Maria Franca Mulas; Francesca Sanna; Marirosa Putzolu; Rosa Rita Bonatesta; Anna Gasperi-Campani; Laura Roncuzzi; Daniela Baiocchi; Sandra Dessì
Cholesterol esterification by acyl‐CoA:cholesterol acyltransferase (ACAT) and proliferation of vascular smooth muscle cells (VSMC) are key events in vascular proliferative diseases. Here we performed experiments to ascertain the role of cholesterol ester pathway in the control of human aortic VSMC cycle progression. Results showed that serum‐induced VSMC proliferation was preceded by an increased ability of the cells to esterify cholesterol as well as by an increased expression of ACAT and multidrug resistance (MDR1) mRNAs and extracellular related kinases 1/2 (ERK1/2), whereas caveolin‐1 levels were markedly decreased. Cell cycle analyses performed in the presence of two inhibitors of cholesterol esterification, directly inhibiting ACAT (Sandoz 58–035) or the transport of cholesterol substrate from plasma membrane to endoplasmic reticulum (progesterone), indicate that each inhibitor suppressed the serum‐induced DNA synthesis by accumulation of VSMCs in the G1 phase. The effect was associated with a rapid inhibition of ERK1/2 mitogenic signaling pathway; a down‐regulation of cyclin D1, ACAT, and MDR1 mRNA; and an up‐regulation of caveolin‐1. These data provide a plausible link between cholesterol esterification and control of cell cycle G1/S transition, supporting the hypothesis that cholesterol esterification may accelerate the progression of human vascular proliferative diseases by modulating the rate of the VSMC proliferation.
Cell Proliferation | 1999
Barbara Batetta; Alessandra Pani; Marirosa Putzolu; Francesca Sanna; Rr Bonatesta; Simona Piras; O. Spano; Mf Mulas; S. Dessì
Abstract. A positive correlation between cholesterol esterification and growth rate potential was previously found in our laboratory during the growth of CEM and MOLT4 lymphoblastic cells. In the current study, we investigated whether the rates of cholesterol esters synthesis correlate with changes of acyl‐CoAcholesterol acyltransferase (ACAT) mRNA levels and of other genes implied in cholesterol biosynthesis and uptake, such as 3‐hydroxy‐3‐methylglutaryl‐CoA (HMGCoA) reductase and low density lipoprotein (LDL) receptor. The results showed that the more rapid growing CEM cells had lower levels of expression of HMGCoA‐reductase and LDL receptors compared to MOLT4. By contrast, ACAT mRNA levels were higher in CEM cells, further supporting the concept of a possible involvement of cholesterol esters in the regulation of cell growth and division. In this study, high levels of cholesterol esterification and of expression of ACAT gene were also associated with a markedly increased expression of multidrug resistance (MDR1) gene, suggesting that MDR1 activity might contribute to regulate the rate of cell growth and division by modulating intracellular cholesterol ester levels.
Cellular and Molecular Life Sciences | 2001
Barbara Batetta; Mf Mulas; Palmina Petruzzo; Rr Bonatesta; Francesca Sanna; Antonello Cappai; Giovanni Brotzu; S. Dessì
Abstract: Cholesterol esterification and smooth muscle cell (SMC) proliferation are the crucial events in the development of atherosclerotic lesions. The objective of this study was to analyse cholesterol esterification and the expression of MDR1 (multidrug resistance), ACAT (acyl-CoA:cholesterol acyltransferase) and caveolin-1 genes in atherosclerotic and healthy vascular walls, in SMCs obtained from atherosclerotic lesions and saphenous veins. Results demonstrated higher levels of cholesterol esters, ACAT and MDR1 mRNAs and lower levels of caveolin-1 mRNA in atherosclerotic segments compared to adjacent serial sections of the same artery and the corresponding non-atherosclerotic arteries from cadaveric donors. SMCs isolated from atherosclerotic plaques manifested an increased capacity to esterify cholesterol and to grow at a faster rate than SMCs isolated from saphenous veins. In addition, when SMCs from atherosclerotic plaques were cultured in the presence of progesterone, a potent inhibitor of cholesterol esterification, significant growth suppression was observed. An increase in ACAT and MDR1 expression and a concomitant decrease in caveolin-1 expression were also observed in SMCs isolated from atherosclerotic arteries as early as 12 h after serum stimulation. An opposite pattern was found when SMCs were treated with progesterone. These findings support the idea that cholesterol esterification plays a role both in early atherogenesis and in clinical progression of advanced lesions and raise the possibility that the cholesterol ester pathway might directly modulate the proliferation of SMCs.
Neuropharmacology | 2007
Angela Maria Falchi; Barbara Battetta; Francesca Sanna; Marco Piludu; Valeria Sogos; Mariangela Serra; Marta Melis; Martina Putzolu; Giacomo Diaz
One of the main functions of the translocator protein (18 kDa) or TSPO, previously known as peripheral-type benzodiazepine receptor, is the regulation of cholesterol import into mitochondria for steroid biosynthesis. In this paper we show that TSPO ligands induce changes in the distribution of intracellular cholesterol in astrocytes and fibroblasts. NBD-cholesterol, a fluorescent analog of cholesterol, was rapidly removed from membranes and accumulated into lipid droplets. This change was followed by a block of cholesterol esterification, but not by modification of intracellular cholesterol synthesis. NBD-cholesterol droplets were in part released in the medium, and increased cholesterol efflux was observed in [(3)H]cholesterol-prelabeled cells. TSPO ligands also induced a prominent shrinkage and depolarization of mitochondria and depletion of acidic vesicles with cytoplasmic acidification. Consistent with NBD-cholesterol changes, MTT assay showed enhanced accumulation of formazan into lipid droplets and inhibition of formazan exocytosis after treatment with TSPO ligands. The effects of specific TSPO ligands PK 11195 and Ro5-4864 were reproduced by diazepam, which binds with high affinity both TSPO and central benzodiazepine receptors, but not by clonazepam, which binds exclusively to GABA receptor, and other amphiphilic substances such as DIDS and propranolol. All these effects and the parallel immunocytochemical detection of TSPO in potentially steroidogenic cells (astrocytes) and non-steroidogenic cells (fibroblasts) suggest that TSPO is involved in the regulation and trafficking of intracellular cholesterol by means of mechanisms not necessarily related to steroid biosynthesis.
Histochemistry and Cell Biology | 2008
Giacomo Diaz; Barbara Batetta; Francesca Sanna; Sabrina Uda; Camilla Reali; Fabrizio Angius; Marta Melis; Angela Maria Falchi
Lipid droplets (LDs) are fat-storing organelles present in virtually all eukaryotic cells and involved in many aspects of cell biology related to lipid metabolism and cholesterol homeostasis. In this study, we investigated the presence of LDs in proliferating and quiescent (contact-inhibited) 3T3 fibroblasts to verify a correlation with cell growth. LDs were characterized by Nile red staining, positivity to adipophilin and negativity to perilipin. LDs were numerous in proliferating cells, but very few in quiescent cells. However, the fraction of quiescent cells, which resumed proliferation after scratch-wound assay, also resumed the formation of LDs. In proliferating cells, the number of LDs correlated with the DNA content, suggesting a continuous accumulation of LDs during cell growth. These findings were supported by biochemical data showing much higher rates of cholesterol esterification and triglyceride synthesis in proliferating cells. Both filipin staining and the fluorescent cholesterol analog dehydroergosterol revealed the presence of an intense traffic of free cholesterol, mediated by acidic vesicles, in proliferating cells. Nile red ratiometric measurements revealed a different lipid composition of LDs in proliferating and quiescent cells. Changes in the number and composition of LDs were also found in growing cells treated with inhibitors of cholesterol esterification (Sandoz 58-035), endosomal cholesterol efflux (U18666A) and V-ATPase (bafilomycin-A1).
Cell Proliferation | 2002
Barbara Batetta; Rr Bonatesta; Francesca Sanna; Marirosa Putzolu; Mf Mulas; Maria Collu; Sandra Dessì
Abstract. Atherosclerosis is an inflammatory‐fibroproliferative response of the arterial wall involving a complex set of interconnected events where cell proliferation (lymphomonocytes, and endothelial and smooth‐muscle cells) and substantial perturbations of intracellular cholesterol metabolism are considered to be among the main features. Glucose‐6‐phosphate dehydrogenase (G6PD), the key enzyme of the hexose‐monophosphate shunt pathway, is an essential enzyme involved in both cell growth and cholesterol metabolism, raising the question as to whether G6PD deficiency may have metabolic and growth implications in a deficient population. In the present study, we investigated cell growth and cholesterol metabolism in peripheral blood lymphomononuclear cells (PBMC) from G6PD‐normal (n = 5) and ‐deficient (n = 5) subjects stimulated with lectins (phytohaemoagglutinin and Concanavalin A). G6PD activity, DNA ([3H]‐thymidine incorporation) cholesterol synthesis and esterification ([14C]‐acetate and [14C]‐oleate incorporation), and G6PD, HMGCoA reductase and low density lipoprotein (LDL) receptor mRNA levels (RT‐PCR) all increased following lectin stimulation in both normal and G6PD‐deficient cells. However, these parameters were significantly lower in G6PD‐deficient cells (P < 0.05). It is of interest that G6PD‐deficient PBMC, which showed lower expression of G6PD and higher expression of the LDL receptor gene than normal PBMC under basal conditions, exhibited an opposite pattern after stimulation: G6PD and HMGCoA reductase being expressed at significantly higher levels in deficient than in normal cells (P < 0.05). We conclude that the reduced capability of G6PD‐deficient cells to respond to mitogenic stimuli and to synthesize cholesterol esters may represent favourable conditions for reducing the risk of cardiovascular diseases.
Journal of Vascular Research | 1999
Barbara Batetta; Sandra Dessì; Marirosa Putzolu; Francesca Sanna; O. Spano; Maria Franca Mulas; Palmina Petruzzo; Antonello Cappai; Giovanni Brotzu
Recent studies have shown that a membrane p-glycoprotein, encoded by MDR1 gene, is involved in the transport of free cholesterol from the plasma membrane to endoplasmic reticulum, the site of cholesterol esterification by acyl-CoA:cholesterol acyltransferase (ACAT). Moreover, results deriving from our previous studies have shown that the rate of cell proliferation was positively correlated with cholesteryl ester levels as well as with ACAT and MDR1 gene expression. In this study, lipid content and the expression of the genes involved in cholesterol metabolism such as hydroxy-methylglutaryl coenzyme A reductase (HMGCoA-R), low-density lipoprotein receptor (LDL-R), ACAT and MDR1 have been investigated in control and atherosclerotic arteries. The results have shown that the levels of cholesteryl ester increase with the age of cadaveric donors in arteries prone to atherosclerosis (abdominal aorta, superficial femoral artery) and become predominant in advanced atherosclerotic lesions. The mRNA levels of ACAT and MDR1 showed the same age correlation, reaching the highest values in atherosclerotic specimens. These results suggest that MDR1 may be involved in the accumulation of intracellular cholesterol ester levels found in atherosclerotic lesions. Moreover, the levels of HMGCoA-R, LDL-R and ACAT gene expressions progressively increased with the age of cadaveric donors; conversely, in atherosclerotic specimens, the mRNA levels of HMGCoA-R and LDL-R drastically decreased while ACAT gene expression reached its maximum. These findings suggest a reactivation of normal homeostatic regulation of cholesterol in advanced and complicated lesions.
Journal of Vascular Research | 2007
Francesca Sanna; Rosa Rita Bonatesta; Bruno Frongia; Sabrina Uda; Sebastiano Banni; Maria Paola Melis; Maria Collu; Clelia Madeddu; Roberto Serpe; Silvana Puddu; Giovanna Porcu; Sandra Dessì; Barbara Batetta
Objective: We have previously demonstrated that Mediterranean glucose-6-phosphate dehydrogenase (G6PD)-deficient peripheral blood mononuclear cells (PBMC) respond to mitogenic stimuli with a reduced cholesterol synthesis and growth. In the present study, we have investigated the release of inflammatory molecules by PBMC following a mitogenic stimulus, as well as the transformation to foam cells of monocyte-derived macrophages from severely G6PD-deficient and normal subjects. Methods and Results: PBMC from G6PD-deficient subjects produced interleukin (IL)-1β and IL-6 to a lower extent compared with normal subjects. 5-Hydroxyeicosatetraenoic acid, a primary product of 5-lipoxygenase, was slightly decreased. Tumour necrosis factor-α and IL-1β secretion was significantly reduced in monocyte-derived macrophages. No difference was found in IL-10 secretion, whereas transforming growth factor-β was invariably found to be significantly higher in G6PD-deficient cells. In cells incubated with acetylated low-density lipoprotein, cholesterol esterification and its storage in lipid droplets were lower than in normal G6PD cells. Conclusions: We conclude that by reducing the secretion of inflammatory molecules by PBMC and increasing the secretion of transforming growth factor-β and the capability of monocyte-derived macrophages to accumulate lipid droplets and convert into foam cells, G6PD deficiency may confer a partial protection against atherosclerosis leading to the reduced risk of cardiovascular diseases reported in G6PD-deficient subjects.
Mediators of Inflammation | 2011
Anna Maria Fulghesu; Francesca Sanna; Sabrina Uda; Roberta Magnini; Elaine Portoghese; Barbara Batetta
Polycystic ovarian syndrome (PCOS) is frequently characterized by obesity and metabolic diseases including hypertension, insulin resistance, and diabetes in adulthood, all leading to an increased risk of atherosclerosis. The present study aimed to evaluate serum and production of inflammatory markers in adolescent Sardinian PCOS. On the basis of HOMA findings, patients were divided into noninsulin resistant (NIR) and insulin resistant (IR), and were weight- and age-matched with healthy girls. Inflammatory cytokines (TNF-α, IL-6, Il-10, TGF-β) and lipokines (leptin, adiponectin), the reactant hs-CRP, and in vitro inflammatory lympho-monocyte response to microbial stimulus were evaluated. In healthy and PCOS subjects, leptin and hs-CRP were correlated with BMI, whereas adiponectin was significantly reduced in all PCOS groups. Although cytokines were similar in all groups, Interleukin-6 (IL-6) was significantly higher in IR PCOS. Moreover, in the latter group lipopolysaccharide-activated monocytes secreted significantly higher levels of IL-6 compared to NIR and control subjects. To conclude, IR PCOS displayed increased IL-6 serum levels and higher secretion in LPS-activated monocytes, whilst revealing no differences for other inflammatory cytokines. These results suggest that in PCOS patients an altered immune response to inflammatory stimuli is present in IR, likely contributing towards determining onset of a low grade inflammation.