Omega-6 polyunsaturated fatty acids prevent atherosclerosis development in LDLr-KO mice, in spite of displaying a pro-inflammatory profile similar to trans fatty acids

Abstract The development of atherosclerosis and the inflammatory response were investigated in LDLr-KO mice on three high-fat diets (40% energy as fat) for 16 weeks: trans (TRANS), saturated (SAFA) or ω-6 polyunsaturated (PUFA) fats. The following parameters were measured: plasma lipids, aortic root...

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Veröffentlicht in:Atherosclerosis 2012-09, Vol.224 (1), p.66-74
Hauptverfasser: Machado, Roberta M, Nakandakare, Edna R, Quintao, Eder C.R, Cazita, Patricia M, Koike, Marcia K, Nunes, Valeria S, Ferreira, Fabiana D, Afonso, Milessa S, Bombo, Renata P.A, Machado-Lima, Adriana, Soriano, Francisco G, Catanozi, Sergio, Lottenberg, Ana Maria
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container_end_page 74
container_issue 1
container_start_page 66
container_title Atherosclerosis
container_volume 224
creator Machado, Roberta M
Nakandakare, Edna R
Quintao, Eder C.R
Cazita, Patricia M
Koike, Marcia K
Nunes, Valeria S
Ferreira, Fabiana D
Afonso, Milessa S
Bombo, Renata P.A
Machado-Lima, Adriana
Soriano, Francisco G
Catanozi, Sergio
Lottenberg, Ana Maria
description Abstract The development of atherosclerosis and the inflammatory response were investigated in LDLr-KO mice on three high-fat diets (40% energy as fat) for 16 weeks: trans (TRANS), saturated (SAFA) or ω-6 polyunsaturated (PUFA) fats. The following parameters were measured: plasma lipids, aortic root total cholesterol (TC), lesion area (Oil Red-O), ABCA1 content and macrophage infiltration (immunohistochemistry), collagen content (Picrosirius-red) and co-localization of ABCA1 and macrophage (confocal microscopy) besides the plasma inflammatory markers (IL-6, TNF-α) and the macrophage inflammatory response to lipopolysaccharide from Escherichia coli (LPS). As expected, plasma TC and TG concentrations were lower on the PUFA diet than on TRANS or SAFA diets. Aortic intima macrophage infiltration, ABCA1 content, and lesion area on PUFA group were lower compared to TRANS and SAFA groups. Macrophages and ABCA1 markers did not co-localize in the atherosclerotic plaque, suggesting that different cell types were responsible for the ABCA1 expression in plaques. Compared to PUFA, TRANS and SAFA presented higher collagen content and necrotic cores in atherosclerotic plaques. In the artery wall, TC was lower on PUFA compared to TRANS group; free cholesterol was lower on PUFA compared to TRANS and SAFA; cholesteryl ester concentration did not vary amongst the groups. Plasma TNF-α concentration on PUFA and TRANS-fed mice was higher compared to SAFA. No difference was observed in IL-6 concentration amongst groups. Regarding the macrophage inflammatory response to LPS, TRANS and PUFA presented higher culture medium concentrations of IL-6 and TNF-α as compared to SAFA. The PUFA group showed the lowest amount of the anti-inflammatory marker IL-10 compared to TRANS and SAFA groups. In conclusion, PUFA intake prevented atherogenesis, even in a pro-inflammatory condition.
doi_str_mv 10.1016/j.atherosclerosis.2012.06.059
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The following parameters were measured: plasma lipids, aortic root total cholesterol (TC), lesion area (Oil Red-O), ABCA1 content and macrophage infiltration (immunohistochemistry), collagen content (Picrosirius-red) and co-localization of ABCA1 and macrophage (confocal microscopy) besides the plasma inflammatory markers (IL-6, TNF-α) and the macrophage inflammatory response to lipopolysaccharide from Escherichia coli (LPS). As expected, plasma TC and TG concentrations were lower on the PUFA diet than on TRANS or SAFA diets. Aortic intima macrophage infiltration, ABCA1 content, and lesion area on PUFA group were lower compared to TRANS and SAFA groups. Macrophages and ABCA1 markers did not co-localize in the atherosclerotic plaque, suggesting that different cell types were responsible for the ABCA1 expression in plaques. Compared to PUFA, TRANS and SAFA presented higher collagen content and necrotic cores in atherosclerotic plaques. In the artery wall, TC was lower on PUFA compared to TRANS group; free cholesterol was lower on PUFA compared to TRANS and SAFA; cholesteryl ester concentration did not vary amongst the groups. Plasma TNF-α concentration on PUFA and TRANS-fed mice was higher compared to SAFA. No difference was observed in IL-6 concentration amongst groups. Regarding the macrophage inflammatory response to LPS, TRANS and PUFA presented higher culture medium concentrations of IL-6 and TNF-α as compared to SAFA. The PUFA group showed the lowest amount of the anti-inflammatory marker IL-10 compared to TRANS and SAFA groups. In conclusion, PUFA intake prevented atherogenesis, even in a pro-inflammatory condition.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/j.atherosclerosis.2012.06.059</identifier><identifier>PMID: 22809447</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ireland Ltd</publisher><subject>ABCA1 ; Animals ; Aorta - metabolism ; atherogenesis ; Atherosclerosis ; Atherosclerosis (general aspects, experimental research) ; Atherosclerosis - metabolism ; Atherosclerosis - pathology ; Atherosclerosis - prevention &amp; control ; ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters - biosynthesis ; Biological and medical sciences ; Blood and lymphatic vessels ; blood lipids ; Cardiology. Vascular system ; Cardiovascular ; cholesterol ; Cholesterol - blood ; collagen ; Collagen - metabolism ; culture media ; Diet, High-Fat ; Dietary Fats, Unsaturated - metabolism ; Dietary Fats, Unsaturated - therapeutic use ; energy ; Escherichia coli ; Fatty acids ; Fatty Acids, Omega-6 - therapeutic use ; high fat diet ; immunohistochemistry ; Inflammation ; Inflammation - metabolism ; Inflammation - prevention &amp; control ; interleukin-10 ; Interleukin-10 - metabolism ; interleukin-6 ; Interleukin-6 - metabolism ; lipopolysaccharides ; macrophages ; Macrophages - physiology ; Male ; Medical sciences ; Mice ; Mice, Knockout ; microscopy ; oils ; omega-6 fatty acids ; polyunsaturated fatty acids ; Receptors, LDL - deficiency ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; Saturated fatty acids ; Trans fatty acids ; Trans Fatty Acids - pharmacology ; tumor necrosis factor-alpha ; Tumor Necrosis Factor-alpha - metabolism ; Unsaturated fatty acids</subject><ispartof>Atherosclerosis, 2012-09, Vol.224 (1), p.66-74</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2012 Elsevier Ireland Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Ireland Ltd. 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The following parameters were measured: plasma lipids, aortic root total cholesterol (TC), lesion area (Oil Red-O), ABCA1 content and macrophage infiltration (immunohistochemistry), collagen content (Picrosirius-red) and co-localization of ABCA1 and macrophage (confocal microscopy) besides the plasma inflammatory markers (IL-6, TNF-α) and the macrophage inflammatory response to lipopolysaccharide from Escherichia coli (LPS). As expected, plasma TC and TG concentrations were lower on the PUFA diet than on TRANS or SAFA diets. Aortic intima macrophage infiltration, ABCA1 content, and lesion area on PUFA group were lower compared to TRANS and SAFA groups. Macrophages and ABCA1 markers did not co-localize in the atherosclerotic plaque, suggesting that different cell types were responsible for the ABCA1 expression in plaques. Compared to PUFA, TRANS and SAFA presented higher collagen content and necrotic cores in atherosclerotic plaques. In the artery wall, TC was lower on PUFA compared to TRANS group; free cholesterol was lower on PUFA compared to TRANS and SAFA; cholesteryl ester concentration did not vary amongst the groups. Plasma TNF-α concentration on PUFA and TRANS-fed mice was higher compared to SAFA. No difference was observed in IL-6 concentration amongst groups. Regarding the macrophage inflammatory response to LPS, TRANS and PUFA presented higher culture medium concentrations of IL-6 and TNF-α as compared to SAFA. The PUFA group showed the lowest amount of the anti-inflammatory marker IL-10 compared to TRANS and SAFA groups. In conclusion, PUFA intake prevented atherogenesis, even in a pro-inflammatory condition.</description><subject>ABCA1</subject><subject>Animals</subject><subject>Aorta - metabolism</subject><subject>atherogenesis</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - pathology</subject><subject>Atherosclerosis - prevention &amp; control</subject><subject>ATP Binding Cassette Transporter 1</subject><subject>ATP-Binding Cassette Transporters - biosynthesis</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>blood lipids</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular</subject><subject>cholesterol</subject><subject>Cholesterol - blood</subject><subject>collagen</subject><subject>Collagen - metabolism</subject><subject>culture media</subject><subject>Diet, High-Fat</subject><subject>Dietary Fats, Unsaturated - metabolism</subject><subject>Dietary Fats, Unsaturated - therapeutic use</subject><subject>energy</subject><subject>Escherichia coli</subject><subject>Fatty acids</subject><subject>Fatty Acids, Omega-6 - therapeutic use</subject><subject>high fat diet</subject><subject>immunohistochemistry</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - prevention &amp; control</subject><subject>interleukin-10</subject><subject>Interleukin-10 - metabolism</subject><subject>interleukin-6</subject><subject>Interleukin-6 - metabolism</subject><subject>lipopolysaccharides</subject><subject>macrophages</subject><subject>Macrophages - physiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>microscopy</subject><subject>oils</subject><subject>omega-6 fatty acids</subject><subject>polyunsaturated fatty acids</subject><subject>Receptors, LDL - deficiency</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><subject>Saturated fatty acids</subject><subject>Trans fatty acids</subject><subject>Trans Fatty Acids - pharmacology</subject><subject>tumor necrosis factor-alpha</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Unsaturated fatty acids</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks9u1DAQxiMEokvhFcCXShzIYjuOkxxAQgUKYqU9lJ6tqTNevDh_ajuV8kS8Jg67VGhPXGxp8puZL9_nLLtgdM0ok2_3a4g_0A9Bu-W0Yc0p42sq17RsHmUrVldNzkQtHmcrSjnLG1bSs-xZCHtKqahY_TQ747ymjRDVKvu17XAHuSTj4OapDxAnDxFbYiDGmYC2bSCjx3vsIznZTNpUdsPYLd9sTzYfNz7_tiWd1fhmKYTRRiSDIa0No4PZ9jsCadqQ29446DqIg5-XgrEOSbCddeBJHEj00Id_NTzPnhhwAV8c7_Ps5vOn75df8s326uvlh02uJWtiLlsqDTNNBbKRpk2_CFSwqpKCl_yWQamFboHTRksqS1EKTmmLwDjSUpqiLs6z14e5SdTdhCGqzgaNzkGPwxQUo0XJqCj_oO8OqE5uBI9Gjd524OcEqSUrtVcnjqklK0WlSlml_pfHVdNth-1D999wEnBxBCBocCZ5otOMB04WhZRcJO7VgTMwKNj5xNxcp03lEnhdVYvUqwOBybp7i14FbbHX2FqPOqp2sP8t-v3JJO1sb5O8nzhj2A-T71M-iqmQetT18gSXF8iS0aIQtPgN36nc9Q</recordid><startdate>20120901</startdate><enddate>20120901</enddate><creator>Machado, Roberta M</creator><creator>Nakandakare, Edna R</creator><creator>Quintao, Eder C.R</creator><creator>Cazita, Patricia M</creator><creator>Koike, Marcia K</creator><creator>Nunes, Valeria S</creator><creator>Ferreira, Fabiana D</creator><creator>Afonso, Milessa S</creator><creator>Bombo, Renata P.A</creator><creator>Machado-Lima, Adriana</creator><creator>Soriano, Francisco G</creator><creator>Catanozi, Sergio</creator><creator>Lottenberg, Ana Maria</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20120901</creationdate><title>Omega-6 polyunsaturated fatty acids prevent atherosclerosis development in LDLr-KO mice, in spite of displaying a pro-inflammatory profile similar to trans fatty acids</title><author>Machado, Roberta M ; Nakandakare, Edna R ; Quintao, Eder C.R ; Cazita, Patricia M ; Koike, Marcia K ; Nunes, Valeria S ; Ferreira, Fabiana D ; Afonso, Milessa S ; Bombo, Renata P.A ; Machado-Lima, Adriana ; Soriano, Francisco G ; Catanozi, Sergio ; Lottenberg, Ana Maria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c619t-6d06f1f97a696fd447a0417764252b1a5c4cda209c6065454200dea12e056f383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>ABCA1</topic><topic>Animals</topic><topic>Aorta - metabolism</topic><topic>atherogenesis</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Atherosclerosis - metabolism</topic><topic>Atherosclerosis - pathology</topic><topic>Atherosclerosis - prevention &amp; control</topic><topic>ATP Binding Cassette Transporter 1</topic><topic>ATP-Binding Cassette Transporters - biosynthesis</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>blood lipids</topic><topic>Cardiology. 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The following parameters were measured: plasma lipids, aortic root total cholesterol (TC), lesion area (Oil Red-O), ABCA1 content and macrophage infiltration (immunohistochemistry), collagen content (Picrosirius-red) and co-localization of ABCA1 and macrophage (confocal microscopy) besides the plasma inflammatory markers (IL-6, TNF-α) and the macrophage inflammatory response to lipopolysaccharide from Escherichia coli (LPS). As expected, plasma TC and TG concentrations were lower on the PUFA diet than on TRANS or SAFA diets. Aortic intima macrophage infiltration, ABCA1 content, and lesion area on PUFA group were lower compared to TRANS and SAFA groups. Macrophages and ABCA1 markers did not co-localize in the atherosclerotic plaque, suggesting that different cell types were responsible for the ABCA1 expression in plaques. Compared to PUFA, TRANS and SAFA presented higher collagen content and necrotic cores in atherosclerotic plaques. In the artery wall, TC was lower on PUFA compared to TRANS group; free cholesterol was lower on PUFA compared to TRANS and SAFA; cholesteryl ester concentration did not vary amongst the groups. Plasma TNF-α concentration on PUFA and TRANS-fed mice was higher compared to SAFA. No difference was observed in IL-6 concentration amongst groups. Regarding the macrophage inflammatory response to LPS, TRANS and PUFA presented higher culture medium concentrations of IL-6 and TNF-α as compared to SAFA. The PUFA group showed the lowest amount of the anti-inflammatory marker IL-10 compared to TRANS and SAFA groups. In conclusion, PUFA intake prevented atherogenesis, even in a pro-inflammatory condition.</abstract><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>22809447</pmid><doi>10.1016/j.atherosclerosis.2012.06.059</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0021-9150
ispartof Atherosclerosis, 2012-09, Vol.224 (1), p.66-74
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1879-1484
language eng
recordid cdi_proquest_miscellaneous_1035104538
source MEDLINE; Elsevier ScienceDirect Journals
subjects ABCA1
Animals
Aorta - metabolism
atherogenesis
Atherosclerosis
Atherosclerosis (general aspects, experimental research)
Atherosclerosis - metabolism
Atherosclerosis - pathology
Atherosclerosis - prevention & control
ATP Binding Cassette Transporter 1
ATP-Binding Cassette Transporters - biosynthesis
Biological and medical sciences
Blood and lymphatic vessels
blood lipids
Cardiology. Vascular system
Cardiovascular
cholesterol
Cholesterol - blood
collagen
Collagen - metabolism
culture media
Diet, High-Fat
Dietary Fats, Unsaturated - metabolism
Dietary Fats, Unsaturated - therapeutic use
energy
Escherichia coli
Fatty acids
Fatty Acids, Omega-6 - therapeutic use
high fat diet
immunohistochemistry
Inflammation
Inflammation - metabolism
Inflammation - prevention & control
interleukin-10
Interleukin-10 - metabolism
interleukin-6
Interleukin-6 - metabolism
lipopolysaccharides
macrophages
Macrophages - physiology
Male
Medical sciences
Mice
Mice, Knockout
microscopy
oils
omega-6 fatty acids
polyunsaturated fatty acids
Receptors, LDL - deficiency
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Saturated fatty acids
Trans fatty acids
Trans Fatty Acids - pharmacology
tumor necrosis factor-alpha
Tumor Necrosis Factor-alpha - metabolism
Unsaturated fatty acids
title Omega-6 polyunsaturated fatty acids prevent atherosclerosis development in LDLr-KO mice, in spite of displaying a pro-inflammatory profile similar to trans fatty acids
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