Dietary Alpha-Linolenic Acid Does Not Protect From Venous Thrombosis In The Vena Cava Stenosis Model

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major causes of cardiovascular morbidity and mortality. Omega-3 fatty acids (n-3 FA) are well known for their beneficial effects on primary and secondary prevention of cardiovascular disease (CVD). We and others have previously reported that n-3 FA, particularly the plant-derived alpha-linolenic acid (ALA), inhibits atherosclerosis, reduces arterial thrombosis and decreases platelet activation in mice fed an n-3-enriched diet by antiinflammatory, antiplatelet and anticoagulant mechanisms. In this study we investigated the effects of ALA on the development of DVT in the vena cava stenosis model in mice.

Hypothesis

Because platelet activation and inflammatory processes may play a relevant role in venous thromboembolism, we hypothesized that ALA prevents the development of venous thrombosis in mice undergoing vena cava stenosis due to its antiplatelet, anticoagulant and antiinflammatory properties.

12 to 14 weeks old C57/BL6 mice underwent 4 weeks of high- (7.3g%; hiALA) or low-ALA (0.03g%; loALA) treatment (n=11 per group) before they were exposed to vena cava stenosis. Rodents were anaesthetized, the inferior vena cava (IVC) was exposed and a ligature was placed proximal to the left renal vein in order to narrow the IVC and to provoke a reduction in blood flow and thereby induce thrombus formation. Mice were examined 48 hours after initial surgery; percentage of mice with thrombus formation and thrombus length were determined. Additionally, we performed blood count analysis and determined plasma glycocalicin index (ug/ml/250 000 platelets), the extramembranous portion of GPIbalpha, as a marker for platelet turnover and shedding of the platelet receptor for von Willebrand factor (vWF).

Contrary to our hypothesis, treatment with ALA did neither significantly reduce the incidence (hiALA, 55 % vs loALA, 64 %; n=11 per group, p=ns) nor size of venous thrombosis (hiALA, 2.4 mm vs loALA, 2.3 mm; n=11 per group, p=ns). Glycocalicin index was comparable in both groups (hiALA, 15.0±8.1 ug/ml/250 000 platelets vs loALA, 11.1±4.5 ug/ml/250 000 platelets; n=8 per group, p=ns), indicating no difference in platelet consumption. Interestingly, we observed an increased leukocyte count and a reduced platelet count in hiALA-treated mice after 48 hours of venous thrombosis, a difference that was not observed in sham operated mice.

Dietary ALA did not protect from DVT in the mouse model of vena cava stenosis chosen. Despite its protective properties in arterial thrombosis, ALA seems to be ineffective in the pathogenesis of the stenosis-induced venous thrombosis, possibly because the pathways of platelet activation and inflammation, modified by ALA, are of lower penetrance. The findings of increased leukocyte count and decreased platelet count after 48 h of VT warrant further investigation.

No relevant conflicts of interest to declare.