High Density Lipoprotein Dysfunctionality in Venous Thromboembolism

Abstract

Venous thromboembolism (VTE) is complex multi‐factorial cardiovascular disease that encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE) and has a high incidence in several populations across the world with unknown pathophysiological mechanism driven by various environmental, acquired and inherited risk factors. DVT, a condition where a blood clot forms inside deeply situated veins in the body (usually in the lower limbs) is very common among Indian population. Lipoproteins modulate the expression and function of coagulation/fibrinolytic factors in patients of various cardiovascular diseases. HDL associated proteins have been proven to show antioxidant, anti‐inflammatory and anti‐thrombotic properties. Thus, the present study aims to examine the functionality of HDL in VTE using an animal model and also validating the same in DVT patients.MethodologyA complete stasis model was used for inducing thrombus in Sprague Dawley rats by ligating their Inferior Vena Cava (IVC). Animal experiments were divided into two groups: Ligated group (with IVC ligation) and SHAM Control group (without ligation). D‐Dimer and Prothrombin Fragment (PF) 1+2 levels were checked to confirm thrombus formation. Further, HDL‐associated proteins and other molecules were quantified using their respective ELISA kits. Similar tests were done in a cohort of human patients diagnosed with DVT (confirmed by a color Doppler test) and the results were compared with healthy individuals. All experiments were done in accordance with their respective ethical guidelines.ResultsD‐Dimer, PF 1+2 and inflammatory molecules were significantly higher in the ligated group, confirming the formation of thrombus. HDL associated proteins (APO‐A1, PON‐1, PAF‐AH & S‐1‐P) were significantly lower whereas oxidized lipoproteins (Ox‐HDL and Ox‐LDL) and lipooxygenase enzymes (15/12‐LOX) were found to be higher in the ligated group as compared to the SHAM control group. DVT patients showed a similar trend of D‐Dimer and PF 1+2 as in animals, when compared to healthy individuals. Lipid profile (Total cholesterol, Triglycerides, LDL and HDL) of patients did not show any significant changes albeit levels of HDL associated proteins were lower than those in healthy volunteers, wherein oxidized lipoproteins were significantly higher. A significance level (p‐value) of <0.05 was used for all the tests.Conclusion and DiscussionPositive D‐Dimer test, high PF 1+2 and inflammatory molecules in DVT patients & in the ligated group of animals, confirm the biochemical changes that occur during thrombosis. Low levels of HDL associated proteins and high levels of lipooxygenase enzymes, responsible for lipoprotein oxidation (proven by high levels of oxidised lipoproteins) support the dysfunctional HDL hypothesis in case of VTE. These findings give more insight in understanding the pathophysiology of VTE and might help in disease prevention/diagnosis/treatment.Support or Funding InformationDefence Research and Development Organisation