Serotonin fails to induce proliferation of endothelial cells preloaded with eicosapentaenoic acid and docosahexaenoic acid.
Diets rich in fish oils are associated with a reduced risk of cardiovascular disease including reduction of atherosclerosis and restenosis. We examined the effect of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), major components of fish oils, on serotonin (5HT) stimulated vascular endothelial cells proliferation as a possible mechanism for this vascular protective effect. In this study we demonstrate that 5HT, a known mitogen for vascular endothelial cells, failed to stimulate proliferation of endothelial cells pre-incubated with EPA and DHA. This inhibitory effect was specific for omega-3 fatty acids only and not shared by other fatty acids like oleic acid (monounsaturated) or arachidonic acid (polyunsaturated) or palmitic acid (saturated). When endothelial cells were exposed to EPA and DHA in the ratio present in fish oils, EPA and DHA were shown to act synergistically in inhibiting the proliferative effect of 5HT. These results suggests that one of the mechanisms by which fish oils may confer vascular protective effect is by making the endothelial cells less responsive to mitogenic stimuli of growth factors such as 5HT that are released by aggregating platelets at sites of vascular injury. This inhibition of endothelial cell proliferation may account for the clinically observed effects of fish oil in attenuating the progression of atherosclerotic changes or neointimal proliferation following vascular injury.
Pakala
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Department of Internal Medicine, University of Texas Houston Medical School, Houston 77030, USA.
Pakala
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Sheng
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Benedict
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CR
D000818:Animals; D001011:Aorta / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004285:Dogs; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D008934:Mitogens; D011985:Receptors, Serotonin; D004281:Docosahexaenoic Acids; D012701:Serotonin; D015118:Eicosapentaenoic Acid; D013936:Thymidine