Dietary omega-3, omega-6, and omega-9 unsaturated fatty acids and growth factor and cytokine gene expression in unstimulated and stimulated monocytes. A randomized volunteer study.
Dietary omega-3 fatty acids retard coronary atherosclerosis. Previously, we demonstrated that dietary omega-3 fatty acids reduce platelet-derived growth factor (PDGF)-A and PDGF-B mRNA levels in unstimulated, human mononuclear cells (MNCs). In a randomized, investigator-blinded intervention trial, we have now compared the effect of ingestion of 7 g/d omega-3, omega-6, or omega-9 fatty acids for 4 weeks versus no dietary intervention on PDGF-A, PDGF-B, heparin-bound epidermal growth factor (HB-EGF), monocyte chemoattractant protein-1 (MCP-1), and interleukin-10 gene expression in unstimulated MNCs and in monocytes that were adherence-activated ex vivo in a total of 28 volunteers. In unstimulated MNCs, mRNA steady-state levels of PDGF-A, PDGF-B, and MCP-1 were reduced by 25+/-10%, 31+/-13%, and 40+/-14%, respectively, after omega-3 fatty acid ingestion, as assessed by quantitative polymerase chain reaction (all P<0.05). In monocytes that were adherence-activated ex vivo for 4 and 20 hours, mRNA steady-state levels of PDGF-A, PDGF-B, and MCP-1 were reduced by 25+/-13%, 20+/-15%, and 30+/-8%, respectively (all P<0.05). Interleukin-10 and HB-EGF mRNA steady-state levels were not influenced by omega-3 fatty acid ingestion. Expression of all respective mRNAs in control volunteers or in those ingesting omega-6 or omega-9 fatty acids were not altered. We conclude that human gene expression for PDGF-A, PDGF-B, and MCP-1, factors thought relevant to atherosclerosis, is constitutive, is constant, and can be reduced only by dietary omega-3 fatty acids in unstimulated and adherence-activated monocytes.
Baumann
K H
KH
Medizinische Klinik, Klinikum Innenstadt, University of Munich, Munich, Germany.
Hessel
F
F
Larass
I
I
Müller
T
T
Angerer
P
P
Kiefl
R
R
von Schacky
C
C
D000328:Adult; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000235:genetics; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D018932:Chemokine CCL2; D016207:Cytokines; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D006133:Growth Substances; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D016753:Interleukin-10; D004815:Epidermal Growth Factor