Highlights
- •Lutein correlates inversely IL-6 in plasma of stable coronary artery disease patients.
- •Lutein is taken up by blood mononuclear cells ex vivo.
- •Lutein decreases production and secretion of inflammatory cytokines ex vivo.
- •Lutein has the potential to resolve inflammation in coronary artery disease patients.
Abstract
Background and aims
Many coronary artery disease (CAD) patients exhibit chronic low-grade inflammation.
Carotenoids are anti-oxidants with potential anti-inflammatory properties. Here, we
first assessed relationships between interleukin (IL)-6 and individual carotenoids
in plasma from CAD patients. Based on the results, we proceeded to assess anti-inflammatory
effects of one carotenoid, lutein, in peripheral blood mononuclear cells (PBMCs) from
CAD patients.
Methods
Lutein + zeaxanthin (isomers with lutein being dominant), β-cryptoxanthin, lycopene,
α- and β-carotene and IL-6 were measured in plasma from 134 patients with stable angina
(SA) and 59 patients with acute coronary syndrome. In 42 patients, plasma measurements
were also performed 3 months after coronary intervention. PBMCs from SA patients were
pre-treated with lutein (1, 5 and 25 μM) for 24 h followed by 24 h incubation ± lipopolysaccharide
(LPS). Cell pellets were collected for IL-6, IL-1β and TNF mRNA and intracellular lutein. Cytokine secretion was measured in cell media.
Results
Only lutein + zeaxanthin were inversely correlated with IL-6 in SA patients at baseline
(r = −0.366, p < 0.001) and follow-up (r = −0.546, p < 0.001). Ex vivo, lutein was taken up by PBMCs from SA patients in a dose- and time-dependent manner.
Pre-treatment with lutein dose-dependently lowered LPS-induced secretion of IL-6,
IL-1β (p < 0.01) and TNF (p < 0.05), and also reduced IL-6, IL-1β and TNF mRNA expression (p < 0.05).
Conclusions
Clinical findings highlighted the inverse association between lutein and IL-6 in CAD
patients. Anti-inflammatory effects of lutein in PBMCs from CAD patients were consolidated
in ex vivo experiments. Taken together, these results show that lutein has the potential to
play a role in resolution of chronic inflammation in CAD patients.
Keywords
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References
- Progress and challenges in translating the biology of atherosclerosis.Nature. 2011; 473: 317-325
- C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease.N. Engl. J. Med. 2004; 350: 1387-1397
- Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis.Eur. Heart J. 2014; 35: 578-589
- Dietary inflammatory index and incidence of cardiovascular disease in the PREDIMED study.Nutrients. 2015; 7: 4124-4138
- Components of the Mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease.Eur. J. Clin. Nutr. 2008; 62: 651-659
- Lutein and atherosclerosis: belfast versus toulouse revisited.Med. Hypotheses. 2017; 98: 63-68
- Carotenoids in cardiovascular disease prevention.JSM Atheroscler. 2016; 1: 1002
- C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among United States adults.Eur. J. Clin. Nutr. 2003; 57: 1157-1163
- Correlates of serum lutein + zeaxanthin: findings from the third national health and nutrition examination survey.J. Nutr. 2004; 134: 2387-2394
- Relationships of circulating carotenoid concentrations with several markers of inflammation, oxidative stress, and endothelial dysfunction: the Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) study.Clin. Chem. 2007; 53: 447-455
- Serum carotenoids and markers of inflammation in nonsmokers.Am. J. Epidemiol. 2000; 152: 1065-1071
- Inflammation and biomarkers of micronutrient status.Curr. Opin. Clin. Nutr. Metab. Care. 2016; 19: 458-463
- Inflammation and vascular endothelial activation in an Aboriginal population: relationships to coronary disease risk factors and nutritional markers.Med. J. Aust. 2003; 178: 495-500
- Provitamin A carotenoids are independently associated with matrix metalloproteinase-9 in plasma samples from a general population.J. Intern Med. 2012; 272: 371-384
- Association of serum carotenoids with high molecular weight adiponectin and inflammation markers among Japanese subjects.Clin. Chim. Acta. 2010; 411: 1330-1334
- Serum carotenoids and vitamins in relation to markers of endothelial function and inflammation.Eur. J. Epidemiol. 2004; 19: 915-921
- Associations of plasma carotenoids with risk factors and biomarkers related to cardiovascular disease in middle-aged and older women.Am. J. Clin. Nutr. 2008; 88: 747-754
- Lutein and zeaxanthin concentrations in plasma after dietary supplementation with egg yolk.Am. J. Clin. Nutr. 1999; 70: 247-251
- Six carotenoids in plasma used to assess recommended intake of fruits and vegetables in a controlled feeding study.Eur. J. Clin. Nutr. 2004; 58: 1166-1173
- Oxygenated carotenoid lutein and progression of early atherosclerosis: the Los Angeles atherosclerosis study.Circulation. 2001; 103: 2922-2927
- Progression of carotid intima-media thickness and plasma antioxidants: the Los Angeles Atherosclerosis Study.Arterioscler. Thromb. Vasc. Biol. 2004; 24: 313-319
- Association of serum vitamin levels, LDL susceptibility to oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis. A case-control study. The ARIC Study Investigators. Atherosclerosis Risk in Communities.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1171-1177
- High serum level of lutein may be protective against early atherosclerosis: the Beijing atherosclerosis study.Atherosclerosis. 2011; 219: 789-793
- The effects of lutein on cardiometabolic health across the life course: a systematic review and meta-analysis.Am. J. Clin. Nutr. 2016; 103: 481-494
- A lutein-enriched diet prevents cholesterol accumulation and decreases oxidized LDL and inflammatory cytokines in the aorta of Guinea pigs.J. Nutr. 2011; 141: 1458-1463
- Lutein prevents high fat diet-induced atherosclerosis in ApoE-deficient mice by inhibiting NADPH oxidase and increasing PPAR expression.Lipids. 2015; 50: 261-273
- Anti-inflammatory effects of lutein in retinal ischemic/hypoxic injury: in vivo and in vitro studies.Invest Ophthalmol. Vis. Sci. 2012; 53: 5976-5984
- Macular pigment lutein is antiinflammatory in preventing choroidal neovascularization.Arterioscler. Thromb. Vasc. Biol. 2007; 27: 2555-2562
- The effect of lutein supplementation on blood plasma levels of complement factor D, C5a and C3d.PLoS One. 2013; 8: e73387
- Lutein supplementation leads to decreased soluble complement membrane attack complex sC5b-9 plasma levels.Acta Ophthalmol. 2015; 93: 141-145
- Low plasma levels of oxygenated carotenoids in patients with coronary artery disease.Nutr. Metab. Cardiovasc Dis. 2007; 17: 448-456
- Plasma carotenoids and risk of acute myocardial infarction in the Singapore Chinese Health Study.Nutr. Metab. Cardiovasc Dis. 2011; 21: 685-690
- Solubilization and stabilization of carotenoids using micelles: delivery of lycopene to cells in culture.Lipids. 1999; 34: 1031-1036
- Serum antioxidants, inflammation, and total mortality in older women.Am. J. Epidemiol. 2006; 163: 18-26
- Statins and nitric oxide reduce C-reactive protein production while inflammatory conditions persist.Mol. Immunol. 2006; 43: 891-896
- Statins reduce interleukin-6-induced C-reactive protein in human hepatocytes: new evidence for direct antiinflammatory effects of statins.Arterioscler. Thromb. Vasc. Biol. 2005; 25: 1231-1236
- Effects of simvastatin on proinflammatory cytokines and matrix metalloproteinases in hypercholesterolemic individuals.Inflammation. 2011; 34: 225-230
- Effects of simvastatin and atorvastatin on inflammation markers in plasma.J. Intern Med. 2002; 251: 338-347
- Association of statins with inflammatory cytokines: a population-based Colaus study.Atherosclerosis. 2011; 219: 253-258
- The non-provitamin A carotenoid, lutein, inhibits NF-kappaB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-kappaB-inducing kinase pathways: role of H(2)O(2) in NF-kappaB activation.Free Radic. Biol. Med. 2008; 45: 885-896
- Lutein protects HT-29 cells against Deoxynivalenol-induced oxidative stress and apoptosis: prevention of NF-kappaB nuclear localization and down regulation of NF-kappaB and Cyclo-Oxygenase-2 expression.Free Radic. Biol. Med. 2010; 49: 50-60
- Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats.Invest Ophthalmol. Vis. Sci. 2006; 47: 2562-2568
Article info
Publication history
Published online: May 06, 2017
Accepted:
May 5,
2017
Received in revised form:
April 21,
2017
Received:
February 2,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
