Flaxseed Prevents leukocyte and Platelet Adhesion to Endothelial Cells in Experimental Atherosclerosis by Reducing sVCAM 1 and vWF

We studied the possible effect of flaxseed to prevent leukocytes and platelets adhesion to endothelial cells and to reduce soluble adhesion molecules (sVCAM1) and endothelial integrity markers (vWF) in ovariectomized rats fed a high fat diet. Forty two female Wistar rats were either sham operated or ovariectomized and randomly assigned for 36 weeks to three different diets: (1) low fat diet (8 percent energy as fat); (2) high fat diet (40 percent energy as fat, lard based, lard group); (3) high fat diet enriched with ground flaxseed 15 g/100 g of food (40 percent energy as fat, lard plus flaxseed group).The ovariectomized rats fed with lard plus flaxseeds had significantly lower serum concentrations of sVCAM and vWF, reduced platelet adhesiveness, and lower extent of platelet and leukocyte adherence to endotheliumin the histological evaluation of the aorta as compared to Ovx  plus lard group. In our study, high dose of ground flaxseed incorporated to lard-based diet prevented the progression of atherosclerotic lesions in estrogen deficiency rats by decreasing platelet and endothelium reactivity. Assessment of platelet adhesion, serum soluble adhesion molecule sVCAM, and endothelium integrity molecule vWF could be useful to detect the risk for atherosclerotic lesions in estrogen deficiency states and to estimate the effect of flaxseed supplementation. (Authors abstract)

Previous studies have demonstrated that flaxseed is beneficial in reducing hypercholesterolemia and progression of atherosclerotic lesions in ovarian hormone deficiency. The available data suggest that the cardio protective properties of flaxseed are due potential mechanisms such as antioxidative, anti-inflammatory, and antithrombotic effects. Few studies have been conducted in order to assess the effects of flaxseed components on platelet and endothelial dysfunction.  The adhesion of both leukocytes and platelets to endothelial cells has been implicated in the progression of atherosclerosis and thrombus formation. Endothelial cells express adhesion molecules such as P selectin, E selectin, intercellular adhesion molecule 1 (ICAM 1), and vascular cell adhesion molecule 1 (VCAM 1) on the cell surface that are involved in leukocyte recruitment and platelet adhesion during thrombosis and inflammation. In addition, endothelial cells synthesize plasma proteins such as von Wille brand factor (vWF) for platelet adhesion in thrombosis and soluble molecules such as E selectin and thrombo modulin (TM).
The activated endothelium plays an integral role in the development of atherosclerosis. Circulating monocytes are attracted to the endothelium by chemokines, bind to the adhesion molecules, adhere, and transmigrate to the subendothelial space, where they become macrophages, scavenge oxidized LDL, become foam cells, and contribute to the development
of the fatty streak in the early stage of atherosclerosis. The purpose of this study was to determine the possible effect of flaxseed to prevent leukocytes and platelets adhesion to endothelial cells and to reduce soluble adhesion molecules (sVCAM 1) and endothelial integrity markers (vWF) in ovariectomized rats fed a high fat diet.

Here, the antiatherogenic mechanism of flaxseed enriched diet was investigated in ovariectomized female rats, a model of experimental atherosclerosis. Platelet aggregation significantly increased in lard fed groups as compared to low fat diet groups, while supplementing the diet with flaxseeds significantly decreased platelet aggregation only in Sham group.  The addition of flaxseeds significantly decreased this endothelial marker in Sham and Ovx groups. Serum vWF increased in Ovx groups as compared to Sham groups. The ovariectomized rats fed with lard  plus flaxseeds had significantly lower serum concentrations of vWF as compared to Ovx  plus lard group. The flaxseed addition to the high fat diet led to significant reduction of TG in Sham and Ovx groups. The supplementation of diet with flaxseed significantly decreased non HDL cholesterol in Sham animals and non significantly decreased total cholesterol and non HDL cholesterol in ovariectomized female rats. The histological evaluation of the aorta in ovariectomized group fed with lard  plus flaxseed diet showed a lower extent of platelet and leukocyte adherence to endothelium similar to Sham group.

The addition of ground flaxseed (15 g per 100 g food) to lard based diet significantly reduced platelet adhesion and serum concentrations of endothelial integrity markers (vFW) and prevented the progression of atherosclerotic lesions in estrogen deficiency states. The results clearly demonstrated that the flaxseed diet may protect against atherosclerotic lesions by decreasing platelet reactivity, without lowering effect on serum cholesterol.

Flaxseed significantly reduced platelet adhesion in ovariectomized female rats.  The high flaxseed dose led to the enrichment of platelet membrane phospholipids with large amounts of eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), resulting in decrease platelet reactivity or endothelial activation (by reducing Pselectin concentrations).  In this study, high dose of ground flaxseed incorporated to lard based diet prevented the progression of atherosclerotic lesions in estrogen deficiency rats by decreasing platelet and
endothelium reactivity without serum cholesterol lowering effects. Assessment of platelet adhesion, serum soluble adhesion molecule sVCAM, and endothelium integrity molecule
vWF could be useful to detect the risk for atherosclerotic lesions in estrogen deficiency states and to estimate the effect of flaxseed supplementation.  Supplementing the diet with high doses of ground flaxseed may lower the atheroslerotic risk in postmenopausal women by increasing the vascular wall protection, reducing thrombotic risk and improving lipid metabolism. (Editors comments)