Eicosapentaenoic acid improves endothelial function in hypertriglyceridemic subjects despite increased lipid oxidizability.
BACKGROUND
Epidemiologic investigations suggest that fish oil, which contains eicosapentaenoic acid (EPA), has favorable cardiovascular effects. Fish oil improves endothelial function in subjects with hypercholesterolemia or diabetes. However, controversy persists regarding relationships between primary hypertriglyceridemia and endothelial dysfunction. Moreover, lipoproteins are more susceptible to oxidation in vitro after incorporation of fish oil.


METHODS
We determined the effects of EPA on serum lipids, susceptibility of low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) to oxidation, and endothelial function in hypertriglyceridemic (HTG) subjects. In 8 men with untreated primary hypertriglyceridemia (plasma triglyceride between 150 and 500 mg/dL) and 7 control subjects (triglyceride below 150 mg/dL), forearm blood flow (FBF) responses were tested. In HTG subjects, this was repeated 3 months after initiation of EPA (1800 mg/day). Cu2+-induced oxidation of VLDL and LDL was determined by serial measurement of conjugated dienes. We used lag time, which corresponded to the period when the lipoproteins were resistant to oxidation, as a parameter of oxidizability. FBF responses to acetylcholine and sodium nitroprusside were determined by strain-gauge plethysmography.


RESULTS
Plasma triglyceride in HTG subjects fell 31% with EPA supplementation. Before EPA, VLDL and LDL lag times in HTG subjects were shorter than in control subjects. EPA further reduced lag time for VLDL but not LDL. The FBF response to acetylcholine (but not to nitroprusside) was significantly less in HTG subjects before EPA than in control subjects. EPA normalized the FBF response to acetylcholine.


CONCLUSIONS
EPA improves endothelial function in HTG subjects despite increasing in VLDL oxidizability.
Okumura
Takahiro
T
Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Fujioka
Yoshio
Y
Morimoto
Shinji
S
Tsuboi
Sayaka
S
Masai
Miho
M
Tsujino
Takeshi
T
Ohyanagi
Mitsumasa
M
Iwasaki
Tadaaki
T
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000097:blood / Q000737:chemistry / Q000187:drug effects; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013995:Time; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D008055:Lipids; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D014665:Vasodilator Agents; D009599:Nitroprusside; D015118:Eicosapentaenoic Acid; D000109:Acetylcholine