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Mechanisms responsible for inhibition of vein-graft arteriosclerosis by fish oil
G E Sarris1, J I Fann, M H Sokoloff
1Department of Cardiovascular Surgery, Stanford University School of Medicine, California 94305.
Abstract:
Favorable changes in lipoproteins, inhibition of platelet aggregation, reduction of serum thromboxane (TX), altered plasma-membrane fluidity, and reduced production of growth factors (mitogens) have all been implicated as possibly being involved in the inhibition of arteriosclerosis by fish oil (FO), which is rich in omega 3 fatty acids; however, causal relations are mostly lacking. Several putative mechanisms responsible for the salutary effects of FO were investigated in a canine model of accelerated vein-graft arteriosclerosis. Venoarterial autografts (N = 192) were implanted in 48 hypercholesterolemic dogs divided into six groups: group A, control; B, FO (as MaxEPA, 200 mg/kg/day eicosapentaenoic acid); C, aspirin (ASA, 50 mg/kg/day); D, TX synthetase inhibitor (TXSI [CGS-12970], 10 mg/kg/day); E, FO + ASA; and F, FO + TXSI. At sacrifice 3 months later, there was no significant difference in plasma lipoproteins, hepatic low density lipoprotein-receptor concentration, red blood cell fragility, bleeding time, or platelet count compared with controls; the decrease in platelet aggregation (30 +/- 5% [mean +/- SEM]) was similar in all treatment groups. Arterialized vein-graft intimal thickening was significantly inhibited by FO (with or without ASA), while ASA alone was ineffective. Conversely, serum TX was significantly lower only in the ASA and FO + ASA groups. Serum mitogenic activity was higher at 3 months in the control group versus all treatment groups. Compared with baseline values, serum mitogenic activity rose significantly over time in the control and the TXSI groups, and an increase or rising trend was present in all other treatment groups except for the FO-treated animals. Thus, the salutary biologic effect of FO in this hypercholesterolemic model of arterialized vein grafts may have been more related to in vivo inhibition of platelet-mitogen growth factor release than to changes in lipoproteins, low density lipoprotein receptors, platelet function, or eicosanoid metabolism. These observations underscore the need for further studies to clarify the interactions between FO (omega 3 fatty acids) and paracrine cellular mitogenic factors in the context of atherosclerosis prevention.
Insights
Fish oil (FO), rich in omega-3 fatty acids, inhibits arteriosclerosis by reducing growth factor release, not by altering lipoproteins or platelet function. Further research is needed to understand FO
Area of Science:
- Cardiovascular Research
- Nutritional Science
- Pharmacology
Background:
- Arteriosclerosis development involves complex mechanisms including lipoproteins, platelet aggregation, and growth factors.
- Fish oil (FO), rich in omega-3 fatty acids, is suggested to inhibit arteriosclerosis, but causal mechanisms remain unclear.
- Understanding FO's effects requires investigating its impact on various biological pathways in relevant models.
Purpose of the Study:
- To investigate the mechanisms underlying the anti-arteriosclerotic effects of fish oil (FO).
- To evaluate the roles of lipoproteins, platelet aggregation, thromboxane (TX), and growth factors in FO's protective action.
- To compare the efficacy of FO alone and in combination with aspirin (ASA) or a TX synthetase inhibitor (TXSI) in a canine model.
Main Methods:
- A canine model of accelerated vein-graft arteriosclerosis was used, involving 192 grafts in 48 hypercholesterolemic dogs.
- Dogs were divided into six groups: control, FO, ASA, TXSI, FO + ASA, and FO + TXSI.
- Measurements included plasma lipoproteins, hepatic LDL-receptor concentration, platelet aggregation, serum TX, and serum mitogenic activity.
Main Results:
- FO significantly inhibited vein-graft intimal thickening, with or without ASA; ASA alone was ineffective.
- Serum TX levels were reduced only in the ASA and FO + ASA groups.
- Serum mitogenic activity was significantly lower in all FO-treated groups compared to controls over time.
Conclusions:
- Fish oil's beneficial effect in preventing vein-graft arteriosclerosis in this model is likely due to inhibiting platelet-mitogen growth factor release.
- These effects are more prominent than changes in lipoproteins, LDL receptors, platelet function, or eicosanoid metabolism.
- Further studies are essential to elucidate the interaction between FO (omega-3 fatty acids) and mitogenic factors in atherosclerosis prevention.