Atherosclerosis Development and Aortic Contractility in Hypercholesterolemic Rabbits Supplemented with Two Different Flaxseed Varieties

Abstract

Alpha-linolenic acid (ALA) is widely regarded as the main beneficial component of flax for the prevention of cardiovascular disease. We evaluated the effect of the transgenic flaxseed W86-which is rich in ALA-on the lipid profile, atherosclerosis progression, and vascular reactivity in hypercholesterolemic rabbits compared to the parental cultivar Linola with a very low ALA content. Rabbits were fed a basal diet (control) or a basal diet supplemented with 1% cholesterol, 1% cholesterol and 10% flaxseed W86, or 1% cholesterol and 10% Linola flaxseed. A high-cholesterol diet resulted in an elevated plasma cholesterol and triglyceride levels compared to the control animals. Aortic sections from rabbits fed Linola had lower deposits of foamy cells than those from rabbits fed W86. A potassium-induced and phenylephrine-induced contractile response was enhanced by a high-cholesterol diet and not influenced by the W86 or Linola flaxseed. Pretreatment of the aortic rings with nitro-L-arginine methyl ester resulted in a concentration-dependent tendency to increase the reaction amplitude in the control and high-cholesterol diet groups but not the flaxseed groups. Linola flaxseed with a low ALA content more effectively reduced the atherosclerosis progression compared with the W86 flaxseed with a high concentration of stable ALA. Aorta contractility studies suggested that flaxseed ameliorated an increased contractility in hypercholesterolemia but had little or no impact on NO synthesis in the vascular wall.

Keywords: Linola usitatissimum L.; aortic contractility; atherosclerosis; cholesterol; genetically modified flaxseed; rabbit model.

Figure 1

Representative photos showing histological cross-sections of thoracic aortae (hematoxylin-eosin staining; magnification, 200×; bar = 50 µm); (A)—control (C) group, normal endothelium and media of the thoracic aorta; (B)—CH group, thick layer of atheromatous plaque in the endothelium of the thoracic aorta; (C)—W group, layer of atheromatous plaque located in the endothelium of the thoracic aorta composed of foam cells, and disintegrated cellular debris; (D)—L group, very thin layer of foamy cells in the endothelium of the thoracic aorta.

Figure 1

Representative photos showing histological cross-sections of thoracic aortae (hematoxylin-eosin staining; magnification, 200×; bar = 50 µm); (A)—control (C) group, normal endothelium and media of the thoracic aorta; (B)—CH group, thick layer of atheromatous plaque in the endothelium of the thoracic aorta; (C)—W group, layer of atheromatous plaque located in the endothelium of the thoracic aorta composed of foam cells, and disintegrated cellular debris; (D)—L group, very thin layer of foamy cells in the endothelium of the thoracic aorta.

Figure 2

Contractile response of rabbit thoracic aortic rings (A) Concentration-response curves to phenylephrine without preincubation; (B) after preincubation with 10 μM L-NAME; (C) after preincubation with 100 μM L-NAME; C—control group; CH—high-cholesterol diet group; W—W86 flaxseed supplemented group; L—Linola flaxseed supplemented group; PHE—phenylephrine; L-NAME—nitro-L-arginine methyl ester; data are expressed as mean ± S.E.M. of the absolute amplitudes of contraction in grams [g]. * indicate values significantly different from results for CH group at a given concentration (p < 0.05); ‘ indicates tendencies (0.05 < p < 1).

Figure 3

Relaxant response of rabbit thoracic aortic rings to sodium nitroprusside after precontraction with phenylephrine. Data are expressed as mean ± S.E.M. of the relative amplitudes of relaxation in % of contraction elicited by 10⁻⁶ M PHE.