Alpha-Linolenic Acid–Rich Wheat Germ Oil Decreases Oxidative Stress and CD40 Ligand in Patients With Mild Hypercholesterolemia
2006; Lippincott Williams & Wilkins; Volume: 26; Issue: 11 Linguagem: Inglês
10.1161/01.atv.0000242795.08322.fb
ISSN1524-4636
AutoresCesare Alessandri, Pasquale Pignatelli, Lorenzo Loffredo, Luisa Lenti, Maria Del Ben, Roberto Carnevale, Alessandro Perrone, Domenico Ferro, Francesco Angelico, Francesco Violi,
Tópico(s)Helicobacter pylori-related gastroenterology studies
ResumoHomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 26, No. 11Alpha-Linolenic Acid–Rich Wheat Germ Oil Decreases Oxidative Stress and CD40 Ligand in Patients With Mild Hypercholesterolemia Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsFree AccessLetterPDF/EPUBAlpha-Linolenic Acid–Rich Wheat Germ Oil Decreases Oxidative Stress and CD40 Ligand in Patients With Mild Hypercholesterolemia Cesare Alessandri, Pasquale Pignatelli, Lorenzo Loffredo, Luisa Lenti, Maria Del Ben, Roberto Carnevale, Alessandro Perrone, Domenico Ferro, Francesco Angelico and Francesco Violi Cesare AlessandriCesare Alessandri From the Department of Experimental Medicine and Pathology, IV Clinical Division, Università di Roma "La Sapienza", Rome, Italy. , Pasquale PignatelliPasquale Pignatelli From the Department of Experimental Medicine and Pathology, IV Clinical Division, Università di Roma "La Sapienza", Rome, Italy. , Lorenzo LoffredoLorenzo Loffredo From the Department of Experimental Medicine and Pathology, IV Clinical Division, Università di Roma "La Sapienza", Rome, Italy. , Luisa LentiLuisa Lenti From the Department of Experimental Medicine and Pathology, IV Clinical Division, Università di Roma "La Sapienza", Rome, Italy. , Maria Del BenMaria Del Ben From the Department of Experimental Medicine and Pathology, IV Clinical Division, Università di Roma "La Sapienza", Rome, Italy. , Roberto CarnevaleRoberto Carnevale From the Department of Experimental Medicine and Pathology, IV Clinical Division, Università di Roma "La Sapienza", Rome, Italy. , Alessandro PerroneAlessandro Perrone From the Department of Experimental Medicine and Pathology, IV Clinical Division, Università di Roma "La Sapienza", Rome, Italy. , Domenico FerroDomenico Ferro From the Department of Experimental Medicine and Pathology, IV Clinical Division, Università di Roma "La Sapienza", Rome, Italy. , Francesco AngelicoFrancesco Angelico From the Department of Experimental Medicine and Pathology, IV Clinical Division, Università di Roma "La Sapienza", Rome, Italy. and Francesco VioliFrancesco Violi From the Department of Experimental Medicine and Pathology, IV Clinical Division, Università di Roma "La Sapienza", Rome, Italy. Originally published1 Nov 2006https://doi.org/10.1161/01.ATV.0000242795.08322.fbArteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2577–2578Epidemiological studies have underlined that a higher intake of α-linolenic acid (18:3n-3) is inversely associated with coronary and carotid atherosclerotic disease.1 Long-chain n-3 fatty acids have been suggested to delay the atherosclerotic process through an antiinflammatory activity2 and in turn to stabilize vulnerable plaque.3 Previous studies suggested, in particular, that n-3 fatty acids may exert an antiinflammatory action by reducing oxidative stress.4 As we have previously shown that oxidative stress is implicated in upregulating CD40 ligand (CD40L), a protein with inflammatory and prothrombotic property,5,6 we tested the hypothesis that 18:3n-3 may protect against atherosclerotic disease also via inhibiting oxidative stress–mediated CD40L expression. To investigate this issue, 32 patients with hypercholesterolemia were randomly allocated, in a double blind fashion, to 2 months supplementation with 2 vegetable oils (1 tbsp/d) containing low (maize oil, 0.63%) or high (wheat germ oil, 8.6%) percentage of 18:3n-3. Before and after treatment oxidative stress and CD40L, a protein that is implicated in the progression of atherosclerotic disease,5 were measured. Also, we analyzed in vitro whether 18:3n-3 fatty acids were able to influence platelet oxidative stress and CD40L expression (for expanded Methods, see supplementary data available online at http://atvb.ahajournals.org).There were no differences in clinical and laboratory characteristics between the 2 groups; after supplementation with both vegetable oils, no change of serum lipid profile was observed (not shown).Maize oil supplementation did not change either soluble CD40 Ligand (sCD40L) data or 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative stress7 (not shown). Conversely, a parallel (r=0.534; P=0.03) and significant decrease of 8-OHdG (from 1.06±0.26 to 0.62±0.20 ng/mL; −41.5%, P<0.001) and sCD40L (from 223.5±32.2 to 96.5±7.1 pg/mL; −56.9%, P<0.001) was seen in wheat germ oil-treated patients. Also, platelet CD40L significantly decreased (mean fluorescence from 45.4±3.1 to 29.3±3.1; −35.4%, P<0.001) only in wheat germ oil-treated patients (Figure, panel A). Download figureDownload PowerPointA, Platelet expression of CD40L (mean fluorescence [MF]) in collagen (6 μg/mL)-stimulated platelets before and after supplementation with maize oil or wheat germ oil in hypercholesterolemic patients. B, Platelet concentration of α-linolenic acid before and after supplementation with maize oil (n=3) or wheat germ oil (n=3) in two subgroups of hypercholesterolemic patients. C, Platelet expression of CD40L (mean fluorescence [MF]). D, production of O2− (stimulation index [SI]). E, Effect of α-linolenic acid on platelet NADPH oxidase activation. Platelet homogenates were added with or without (control) arachidonic acid (AA), (0.5 mmol/L), NADPH(25 μmol/L), or AA plus NADPH with or without α-linolenic acid (n=3 from healthy subjects). F, p38MAP kinase (arbitrary units) activation, in unstimulated platelets (control), and collagen-stimulated platelets (coll) incubated with or without α-linolenic acid (n=3 from healthy subjects). *P<0.002.A significant increase of platelet content of linoleic acid was observed in patients given maize (n=3, +14.28%, P<0.005) or wheat germ oil (n=3, +16%, P<0.05). Conversely, a significant increase of platelet concentration of α-linolenic acid was observed only in patients given wheat germ oil (n=3, +255%, P 0.05 in patients given maize oil; Figure, panel B). Also a significant reduction in platelet arachidonic acid (n=3, −16.5%, P<0.005) was observed only in patients given wheat germ oil. Platelets from volunteers incubated with liposomes containing linoleic acid or α-linolenic acid showed a different behavior. Thus, linoleic acid demonstrated a nonsignificant decrease of CD40L platelet O2−, NADPH oxidase, and p38MAP kinase activation (data not shown); conversely platelets incubated with α-linolenic acid showed a marked reduction of platelet CD40L expression (Figure, panel C), O2− production (Figure, panel D), NADPH oxidase (Figure, panel E), and p38MAP kinase activation (Figure, panel F).This study showed that in patients with hypercholesterolemia, wheat germ oil supplementation was associated with parallel reduction of oxidative stress and platelet CD40L expression suggesting that n-3 fatty acids downregulated CD40L via an oxidative stress–mediated mechanism. In vitro experiments showing that platelet incubation with n-3 fatty acids elicited significant decrease of platelet O2− could support such hypothesis. Moreover, platelets incubated with n-3 fatty acids showed reduced activation of NADPH oxidase and phosphorylation of p38 MAP kinase, which is a protein implicated in the activation of NADPH oxidase.8,9 The underlying mechanism cannot be fully elucidated at the moment. Accumulation of 18:3n-3 on platelet membrane could reduce the content of arachidonic acid and in turn lower NADPH oxidase activation.8 This hypothesis, which is consistent with previous data showing a key role for arachidonic acid in stimulating platelet NADPH oxidase–dependent O2− generation,10 should be investigated in the future.Even if we cannot exclude that the n-3 antioxidant effect could not only be the cause but also the consequence of downregulation of CD40L,10 our hypothesis is consistent with an interventional study showing that supplementation with ascorbic acid was associated with platelet CD40L downregulation.11In conclusion, we provide evidence that wheat germ oil is an important source of n-3 fatty acids, which may exert an antiatherosclerotic effect via inhibition of oxidative stress–mediated CD40L upregulation.AcknowledgmentsWe are grateful to Annarita Scarca and Roberto Petruccioli for the generous gift of wheat germ oil (Germen).Source of FundingThis study was supported in part by a grant from the University of Rome "La Sapienza" (Ateneo 2003).DisclosuresNone.FootnotesCorrespondence to Prof Francesco Violi, Divisione IV Clinica Medica, University "La Sapienza", Viale del Policlinico 161, 00185 Rome, Italy. 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