thromboxane-b2 and Hyperplasia

Previous studies suggest that cyclooxygenase-2 (COX-2) might influence megakaryocyte (MK) maturation and platelet production in vitro. Using a gene deletion model, we analysed the effect of COX-2 deficiency on megakaryopoiesis and platelet function. COX-2-/- mice (10-12 weeks old) have hyper-responsive platelets as suggested by their enhanced aggregation, TXA2 biosynthesis, CD62P and CD41/CD61 expression, platelet-fibrinogen binding, and increased thromboembolic death after collagen/epinephrine injection compared to wild-type (WT). Moreover, increased platelet COX-1 expression and reticulated platelet fraction were observed in COX-2-/- mice while platelet count was similar to WT. MKs were significantly reduced in COX-2-/- bone marrows (BMs), with high nuclear/cytoplasmic ratios, low ploidy and poor expression of lineage markers of maturation (CD42d, CD49b). However, MKs were significantly increased in COX-2-/- spleens, with features of MK maturation markers which were not observed in MKs of WT spleens. Interestingly, the expression of COX-1, prostacyclin and PGE2 synthases and prostanoid pattern were modified in BMs and spleens of COX-2-/- mice. Moreover, COX-2 ablation reduced the percentage of CD49b+ cells, the platelet formation and the haematopoietic stem cells in bone marrow and increased their accumulation in the spleen. Splenectomy decreased peripheral platelet number, reverted their hyper-responsive phenotype and protected COX-2-/- mice from thromboembolism. Interestingly, fibrosis was observed in spleens of old COX-2-/- mice (28 weeks old). In conclusion, COX-2 deletion delays BM megakaryopoiesis promoting a compensatory splenic MK hyperplasia, with a release of hyper-responsive platelets and increased thrombogenicity in vivo. COX-2 seems to contribute to physiological MK maturation and pro-platelet formation.

Topics: Animals; Antigens, CD; Antigens, Differentiation; Blood Platelets; Bone Marrow; Crosses, Genetic; Cyclooxygenase 1; Cyclooxygenase 2; Hematopoietic Stem Cells; Hyperplasia; Megakaryocytes; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Platelet Count; Ploidies; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thromboxane A2, Prostaglandin H2; Spleen; Splenectomy; Thromboembolism; Thrombophilia; Thrombopoiesis; Thromboxane B2

Restenosis is a critical complication of angioplasty and stenting. Restenosis is multifactorial, involving endothelial injury, inflammation, platelet activation, and vascular smooth muscle cell (VSMC) proliferation. Thus, dietary strategies to prevent restenosis likely require the use of more than one agent. Resveratrol (R) and quercetin (Q) are polyphenols that are known to exhibit vascular protective effects. We tested whether R and Q administered in the diet interact to inhibit vessel stenosis in mice with a carotid injury. B6.129 mice were administered a high-fat diet containing 21% fat and 0.2% cholesterol along with R (25 mg/kg), Q (10 mg/kg), or R + Q for 2 wk. A carotid injury was induced and the mice were again administered the enriched diet for 2 wk. Compared with the controls, R significantly decreased stenosis, assessed as an intima:media ratio, by 76%. Although Q treatment alone exhibited no effect, it potentiated the effect of R in that treatment with R + Q significantly decreased the intima:media ratio by 94%. Moreover, this effect was greater than that of R treatment alone (P < 0.05). Although treatments with R, Q, and R + Q significantly affected platelet activation and endothelial function, the responses observed for R + Q were less than additive. Specifically, the effects of R + Q were less than the sum of effects for treatments with R and Q alone. In contrast, treatment with R + Q exhibited more-than-additive effects on inflammatory markers and significant interactions between R and Q were observed. The presence of synergy between R and Q was thus tested in cultures of VSMC and macrophages. Isobolographic analysis revealed that 2:1 molar ratios of R:Q exhibited synergistic inhibition of VSMC proliferation and macrophage chemotaxis. In conclusion, in combination, R and Q can interact to reduce the extent of restenosis, perhaps due to their synergistic inhibition of VSMC proliferation and inflammation.

Topics: Animals; Antioxidants; Carotid Artery Injuries; Cell Proliferation; Chemotaxis; Drug Interactions; Endothelial Cells; Endothelium, Vascular; Female; Hyperplasia; Inflammation; Mice; Monocytes; Neointima; Quercetin; Resveratrol; Stilbenes; Thromboxane B2

To expedite the investigation of new devices for inhibiting restenosis, we aimed to develop a modified model of arterial angioplasty and stenting in rats that showed greater face validity than the traditional rat model.. Carotid arteries from Sprague-Dawley rats fed a normal or an atherogenic diet containing a low dose of cholate underwent balloon pre-dilation followed by placement of a bare metal stent. Vessel patency was followed for 28d using ultrasound. Stented vessels were then harvested and were subjected to histologic analysis. Plasma lipid profiles and biomarkers of endothelial dysfunction, inflammation and thrombosis were assessed.. There was significant interaction between stenting injury and the atherogenic diet, leading to higher levels of markers for inflammation, platelet activation, and endothelial dysfunction, as well as neointimal hyperplasia, compared with stented rats on normal chow. There was a significant correlation between plasma IL-6 and TXB(2) in stented rats, a relationship which may have contributed to exaggerated vessel remodeling with increased platelet sensitivity. Compared to normal chow, the atherogenic diet also increased fibrin and proteoglycan deposition near stent struts.. Arterial stenting, in combination with the atherogenic diet, led to exacerbated endothelial dysfunction, inflammation, platelet activation, and vascular remodeling compared with stented rats on normal chow. By reproducing key features of clinical restenosis that are lacking in other rat models, this modified rat model may serve as a valuable screening tool to rapidly evaluate new coatings and devices before moving candidates into expensive, more time-consuming rabbit or porcine models.

Topics: Angioplasty, Balloon; Animals; Arginine; Biomarkers; Carotid Arteries; Carotid Artery Injuries; Carotid Stenosis; Choline Deficiency; Diet, Atherogenic; Disease Models, Animal; Endothelial Cells; Female; Hyperplasia; Inflammation Mediators; Interleukin-6; Lipids; Male; Platelet Activation; Rats; Rats, Sprague-Dawley; Recurrence; Reproducibility of Results; Stents; Thromboxane B2; Time Factors; Ultrasonography, Doppler, Color

The role of prostacyclin in the development of venous thrombosis and vascular dysfunction in humans is unclear. In patients with deep vein thrombosis (DVT, n=34) and controls (matched for age, sex, indexes of systemic inflammation and metabolic status, n=20), we studied (i) differences on systemic markers of vascular disease and platelet activation and (ii) the influence of prostacyclin receptor gene (PTGIR) polymorphisms.. Enhanced levels of urinary 11-dehydro-thromboxane (TX)B2 and plasma [soluble(s)] P-selectin, mostly platelet derived, were detected in DVT patients, whereas plasma von Willebrand factor levels and intima-media thickness of the common carotid arteries were not significantly different. In all patients' cohorts, we identified five PTGIR polymorphisms (three nonsynonymous: P226T, R212C, V196L; two synonymous: V53V, S328S). In the four individuals carriers of R212C polymorphism (three in DVT, one in controls), intima-media thickness values were significantly (P=0.0043) higher than those detected in individuals of all cohorts [1.68+/-0.38, 1.55 (1.4-2.2) vs. 1.05+/-0.33, 1.08 (0.01-1.68) mm, respectively, mean+/-SD, median (range)]. Moreover, enhanced sP-selectin and 11-dehydro-TXB2, in DVT versus controls, were statistically significant only in carriers of both synonymous PTGIR polymorphisms V53V/S328S. Only the PTGIR mutant R212C was dysfunctional when examined in an in vitro overexpression system.. Our results suggest a propensity of enhanced platelet activation in DVT patients with PTGIR polymorphisms V53V/S328S. Moreover, we identified a dysfunctional PTGIR polymorphism (R212C) associated with intimal hyperplasia.

Topics: Adult; Aged; Biomarkers; Female; Genetic Linkage; Genetic Testing; Humans; Hyperplasia; Male; Middle Aged; P-Selectin; Platelet Activation; Polymorphism, Single Nucleotide; Receptors, Epoprostenol; Thromboxane B2; Tunica Intima; Venous Thrombosis

Vein graft failure within the first month after bypass surgery is largely because of thrombosis. However, systemic study of thrombus formation in vein grafts is still lacking, and few effective techniques are available to prevent this event. Herein, we analyzed the kinetics of thrombosis and tested the effectiveness of locally applied aspirin on prevention of the disease in a mouse model. En face analysis of vein grafts revealed that 67+/-12% and 54+/-17% of the surface areas were covered by microthrombi at 1 and 3 days, respectively. Thrombus generation was also identified by labeling of platelets and fibrin, which occurred in 35 grafts examined at 1 and 3 days and 1, 2, 4, and 8 weeks. In a fifth of grafts, the thrombus occluded the vessel lumen by > or =1/4. Furthermore, a significant loss of endothelial cells was evidenced by beta-gal staining for vein grafts in transgenic mice expressing LacZ gene controlled by TIE2-endothelial specific gene promoter. Following thrombosis, neointimal lesions were significantly increased by 4-fold 2 weeks after the operation. When vein grafts were treated locally with aspirin in pluronic gel-127, the thrombus area was significantly reduced (P<0.005) at 1, 4, and 8 weeks. Interestingly, neointimal lesions were markedly reduced in the local, but not oral, aspirin-treated group at 4 and 8 weeks by 50% to 70% (P<0.005). The mechanism of reduced lesions by locally applied aspirin involved the protection of vein graft endothelium. Thus, we provide strong evidence that thrombus formation occurs before the development of neointimal lesions in vein grafts and that local aspirin treatment successfully reduces vein graft arteriosclerosis through endothelial protection, resulting in reduction of thrombosis.

Topics: Animals; Arteriosclerosis; Aspirin; Blood Vessel Prosthesis Implantation; Carotid Arteries; Disease Models, Animal; Endothelium, Vascular; Fibrinolytic Agents; Graft Occlusion, Vascular; Hyperplasia; Mice; Mice, Knockout; Mice, Transgenic; Platelet Aggregation Inhibitors; Postoperative Complications; Receptor, TIE-2; Thrombosis; Thromboxane B2; Tunica Intima; Venae Cavae

Prostaglandin formation is enhanced in vascular disease, in part through induction of cyclooxygenase (COX-2) in vascular smooth muscle cells. Because COX regulates cell growth and migration, we examined whether the COX expression plays a role in the development of intimal hyperplasia after vascular injury. Rats undergoing balloon angioplasty of the carotid artery were randomized to receive a selective COX-2 inhibitor (SC-236), a selective COX-1 inhibitor (SC-560) or a combination of the two. Normal, uninjured vessels showed COX-1, but no COX-2 expression. Fourteen days after balloon injury, both COX-1 and COX-2 were expressed in the neointima. Balloon angioplasty resulted in a marked increase in the urinary excretion of prostaglandin (PG) E(2,) PGF(2alpha), and thromboxane (TX) B(2). Both the COX-1 inhibitor SC-560 and the COX-2 inhibitor SC-236 suppressed the generation of PGE(2) and PGF(2alpha), particularly when combined, suggesting a role for both isozymes in the generation of prostaglandins in this model. In contrast, TXA(2) was markedly suppressed by the COX-1 inhibitor SC-560. COX-2 inhibition with SC-236 had no effect on intimal hyperplasia at day 14 (0 versus 8.5%; n = 7 in controls). In contrast, intimal hyperplasia was reduced by SC-560 when administered alone (by 42%; n = 7, p < 0.05) or in combination with SC-236 (by 40%; n = 7, p < 0.05). COX-1 may play a role in the development of intimal hyperplasia, potentially through the inhibition of platelet TXA(2). Despite being expressed in the neointima, COX-2 does not play a role in the development of intimal hyperplasia after vascular injury.

Topics: Angioplasty, Balloon; Animals; Carotid Arteries; Cyclooxygenase 1; Dinoprost; DNA Primers; Eicosanoids; Graft Occlusion, Vascular; Hyperplasia; Immunohistochemistry; Isoenzymes; Male; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Thromboxane B2; Tunica Intima

The efficacy of OPC-29030, a newly developed inhibitor of 12(S)-hydroxyeicosatetraenoic acid (12-HETE) production, was evaluated on intimal hyperplasia of experimental autologous vein grafts in a distal poor-runoff model and a hyperlipidemic model in rabbits. First, rabbits were divided into two groups, the distal poor-runoff group (PR group) and the hyperlipidemic group (HL group). After 4 weeks preparing the PR model and the HL model, the femoral vein was implanted into the ipsilateral femoral artery. Then they were subdivided into two groups, depending on the diet provided; diet group with 0.1% OPC-29030 (OPC-29030 group) and normal diet group (control group). At 4 weeks, the grafts were harvested, and intimal hyperplasia of the graft was measured with an ocular cytometer. Intimal cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation at 2 weeks after surgery. In addition, the effect of OPC-29030 on the proliferation or migration of rat aortic smooth muscle cells in culture was investigated. In the in vivo study in the PR group, the intimal hyperplasia and the plasma 12-HETE levels in the OPC-29030 group were significantly inhibited, compared with those of the control group. However, in the HL group, the intimal hyperplasia in both the OPC-29030 and control groups showed a remarkable degree of intimal hyperplasia. There was no significant difference between those two groups. Furthermore, there was no significant difference in the plasma 12-HETE levels in the HL group irrespective of the presence of OPC-29030. The BrdU labeling index at 2 weeks after grafting was significantly lower in the OPC-29030 group compared with that in the control group in the PR group. In the in vitro study, OPC-29030 did not inhibit smooth muscle cell proliferation; however, OPC-29030 inhibited the migration. These results demonstrate the efficacy of OPC-29030 in reducing the degree of intimal hyperplasia under PR conditions, but not under hyperlipidemic conditions. The mechanism of reducing the intimal hyperplasia may be that OPC-29030 inhibited 12-HETE production, which did not inhibit proliferation while inhibiting migration of the smooth muscle cell. These results suggested the possible involvement of 12-HETE with the intimal hyperplasia under PR conditions.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 6-Ketoprostaglandin F1 alpha; Animals; Cells, Cultured; Cholesterol; Femoral Vein; Graft Survival; Hypercholesterolemia; Hyperplasia; Imidazoles; Male; Muscle, Smooth, Vascular; Platelet Aggregation Inhibitors; Quinolones; Rabbits; Rats; Sulfur Compounds; Thromboxane B2; Tunica Intima

Vascular smooth muscle cell (VSMC) proliferation and migration to the subintima or intimal hyperplasia (IH) occur after arterial injury and are thought to be induced by mitogenic factors released from activated platelets. Because low flow (LF) and shear have been attributed to the localization and progression of IH, we postulated that hemodynamic factors may regulate the degree of platelet activation, as measured by plasma thromboxane B2 (TXB2) and platelet-derived growth factor-AB (PDGF-AB) release at regions of experimental arterial injury.. The right common carotid artery (CCA) was subjected to balloon injury in 18 New Zealand White male rabbits. Flow in the injured CCA was reduced by out-flow ligation (LF group, n = 6) or increased by ligation of the left CCA (high flow [HF] group, n = 6). In six other animals, flow was preserved (normal flow [NF] group). Mean blood flow and pressure in the right CCA were measured thereafter at 10 and 30 minutes. Plasma TXB2 and PDGF-AB levels were determined with the enzyme-linked immunosorbent assay method in each animal with blood samples taken systematically before injury (baseline) and in the distal CCA at similar time points.. At 10 minutes, mean blood flow was reduced from 20 +/- 2 ml/min in the NF group to 7 +/- 1 ml/min in the LF group animals (p < 0.01) and increased to 32 +/- 2 ml/min in the HF group animals (p < 0.05). Mean arterial blood pressure did not differ among the groups. Hemodynamic parameters were similar at 10 and 30 minutes. TXB2 levels were more than fourfold greater in the LF group than in the HF and NF groups at both time points (p < 0.05). In addition, there was a twofold increase in plasma PDGF-AB level at 10 minutes in the LF group compared with baseline levels (p < 0.05).. Platelet activation at regions of acute vascular injury was determined to be flow dependent. Upregulated platelet activity in low flow conditions may be due to increased platelet exposure time to subendothelial collagen and is greatly attenuated if normal or increased flow is present.

Topics: Acute Disease; Animals; Blood Flow Velocity; Blood Platelets; Blood Pressure; Carotid Artery Injuries; Carotid Artery, Common; Catheterization; Cell Division; Cell Movement; Collagen; Disease Progression; Enzyme-Linked Immunosorbent Assay; Hemorheology; Hyperplasia; Male; Mitogens; Muscle, Smooth, Vascular; Platelet Activation; Platelet-Derived Growth Factor; Rabbits; Recombinant Proteins; Regional Blood Flow; Thromboxane B2; Time Factors; Tunica Intima; Up-Regulation

Juxtaglomerular (JG) hyperplasia and tubular damage along with a decrease in the urine creatinine level induced by FK506 in rat kidney have already been reported in previous paper by us. In this paper, we document the relationship of FK506 nephrotoxicity to the change in the production of thromboxane (Tx) A2 and the lipid peroxidation of the cellular membrane in the rat kidney in order to clarify its morphogenesis. The urinary excretion of TxB2 increased with FK506 administration even on day 1 (P < 0.02). Histologically, OKY-046 (thromboxane synthetase inhibitor) decreased tubular damage, although JG hyperplasia was not eradicated, while biochemically the excretion of TxB2 decreased significantly (P < 0.02), and both the decrease in the urine creatinine level and the increase in the N-acetyl-beta,D-glucosaminidase (NAG) index were relatively smaller. Although the FK506-induced morphological and biochemical changes could not be prevented by the continuous administration of superoxide dismutase (SOD) 30,000 U/kg daily, the malondialdehyde content in renal tissue removed 1 h after FK506 administration had increased. These data suggest that FK506 nephrotoxicity is related to the change in the production of TxA2 and lipid peroxidation of the cellular membrane. However, other mechanisms such as the involvement of sympathomimetic effects of FK506 and other vasoconstrictive factors cannot be ruled out.

Topics: Acetylglucosaminidase; Animals; Creatinine; Enzyme Inhibitors; Hyperplasia; Kidney; Kidney Tubules, Proximal; Methacrylates; Rats; Superoxide Dismutase; Tacrolimus; Thromboxane B2

To investigate the relative irritant potencies of inhaled aldehydes, guinea pigs were exposed to formaldehyde or acrolein and specific total pulmonary resistance and bronchial reactivity to intravenous acetylcholine were assessed. The mechanisms associated with these responses were investigated by analyzing morphologic and biochemical changes in airway epithelial cells after in vivo and in vitro exposures. Immediately after exposure to formaldehyde or acrolein, specific resistance increased transiently and returned to control values within 30 to 60 minutes. Bronchial hyperreactivity, assessed by the acetylcholine dose necessary to double resistance, increased and became maximal two to six hours after exposure to at least 9 parts per million2 (ppm) formaldehyde or at least 1 ppm acrolein for two hours. The effect of exposure to 3 ppm formaldehyde for two hours was less than the effect of exposure to 1 ppm formaldehyde for eight hours; thus, extended exposures produced a disproportionate heightening of bronchial reactivity. Bronchial hyperreactivity often persisted for longer than 24 hours. Increases in three bronchoconstrictive eicosanoids, prostaglandin F2 alpha, thromboxane B2, and leukotriene C4, occurred immediately after exposure, whereas an influx of neutrophils into lavage fluid occurred 24 hours later. Histological examination of the tracheal epithelium and lamina propria also demonstrated a lack of inflammatory cell infiltration. Treatment with leukotriene synthesis inhibitors and receptor antagonists inhibited acrolein-induced hyperreactivity, supporting a causal role for these compounds in this response. Acrolein also stimulated eicosanoid release from bovine epithelial cells in culture. However, the profile of metabolites formed differed from that found in lavage fluid after in vivo exposure. Similarly, human airway epithelial cells did not produce cysteinyl leukotriene or thromboxane B2. However, cysteinyl leukotrienes were mitogenic for human airway epithelial cells in a concentration-dependent manner and exhibited a structure-activity relationship; leukotriene C4 was more potent than its sequential metabolites D4 and E4. The potency of leukotriene C4 was striking, stimulating colony-forming efficiency in concentrations as low as 0.01 pM. Together, these findings suggest that environmentally relevant concentrations of aldehydes can induce bronchial hyperreactivity in guinea pigs through a mechanism involving injury to cells present in the air

Topics: Acetylcholine; Acrolein; Air Pollutants; Airway Resistance; Animals; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Epithelium; Epoprostenol; Formaldehyde; Guinea Pigs; Hyperplasia; Inflammation; Leukocyte Count; Leukotriene B4; Lipoxygenase Inhibitors; Neutrophils; Phenothiazines; Phenylbutyrates; Prostaglandins F; SRS-A; Thromboxane B2; Time Factors

The effect of purified eicosapentanoic acid on intimal fibrous hyperplasia in expanded polytetrafluoroethylene grafts was examined in 18 rabbits undergoing infrarenal aorta reconstruction. Six rabbits received commercial rabbit chow (control group), six a regular diet supplemented with 1% cholesterol (cholesterol group), and six the cholesterol diet with 91.1% pure eicosapentanoic acid 500 mg/day (eicosapentanoic acid group). Grafts were harvested 3 months after surgery for histologic examination. The platelet count and serum beta-thromboglobulin and platelet factor 4 concentrations were not significantly different between groups. Serum arachidonic acid level in the cholesterol group was significantly higher than in the control group, and serum eicosapentanoic acid levels in the eicosapentanoic acid group were significantly higher than in the remaining two groups. Intergroup differences in serum 6-keto-prostaglandin F1 alpha and thromboxane B2 concentrations were not significant. Intimal thickness at midgraft was 5.2 +/- 6.2 microns in the control group, 67.6 +/- 46.9 microns in the cholesterol group, and 19.2 +/- 18.4 microns in the eicosapntanoic acid group. intimal thickness in the cholesterol group was greater than in either the control or licosapentanoic acid group (p less than 0.01 and p less than 0.05, respectively). These data suggest that eicosapentanoic acid reduces intimal fibrous proliferation in expanded polytetrafluoroethylene grafting as a result of hypercholesterolemia and that this effect is independent of the platelet count, activated platelet factors, and the prostacyclin/thromboxane A2 ratio.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta, Abdominal; Arachidonic Acid; Arachidonic Acids; beta-Thromboglobulin; Blood Vessel Prosthesis; Cholesterol, Dietary; Eicosapentaenoic Acid; Elastic Tissue; Endothelium, Vascular; Hypercholesterolemia; Hyperplasia; Male; Platelet Count; Platelet Factor 4; Polytetrafluoroethylene; Rabbits; Radiography; Thromboxane B2; Wound Healing

The effects of low-dose cod-liver oil on intimal hyperplasia of vein grafts were examined in 45 adult mongrel dogs undergoing peripheral arterial reconstruction. Fifteen animals served as the control group, 15 animals were fed a fish-oil supplement containing 240 mg of eicosapentaenoic acid daily, and a further 15 animals received 480 mg of eicosapentaenoic acid daily. Segments of undistended external jugular vein were anastomosed to bilaterally divided femoral arteries. The grafts were harvested at 6 weeks and intimal thickness was measured with a computerized interactive image analyzing system. Serum cholesterol level, prothrombin time, partial thromboplastin time, bleeding time, and platelet counts were measured before the operation and at 2, 4, and 6 weeks after the operation. Plasma levels of thromboxane B2 and prostaglandin F1 alpha and serum levels of eicosapentaenoic acid were measured before and 4 weeks after the operation. Serum cholesterol level increased similarly and significantly in all animals. Serum levels of eicosapentaenoic acid rose proportionately with the oral ingestion of fish oil but did not affect coagulation parameters. Plasma thromboxane B2 and prostaglandin F1 alpha were not significantly affected by the ingestion of marine oils. Intimal thickness was 39 +/- 5 microns in the control dogs. Ingestion of 240 mg of eicosapentaenoic acid reduced intimal thickness to 24 +/- 3 microns at 6 weeks (p less than 0.01). Increasing the dose by a factor of 2 did not decrease intimal thickness further, the intima being 23 +/- 2 microns (p less than 0.005). Our data indicate that small doses of fish oil will reduce intimal proliferation in autologous vein grafts and that marine oils may exert their beneficial effects on intimal hyperplasia by a mechanism other than their known effects on prostanoid metabolism.

Topics: Animals; Blood Vessel Prosthesis; Cod Liver Oil; Dogs; Eicosapentaenoic Acid; Femoral Artery; Fish Oils; Hyperplasia; Jugular Veins; Muscle, Smooth, Vascular; Prostaglandins F; Thromboxane B2; Transplantation, Autologous