Pathophysiology of Venous Thromboembolism: Putative role of HDL
Authors: Kumar Vinay , Garg Iti , Srivastava Swati , Ganju Lilly , Varshney Rajeev 
Published: May 2022

Introduction

In 2019, cardiovascular disease (CVD) was the main reason of all global deaths (32%) and out of these deaths, 85% were due to heart attack and stroke alone. Venous thromboembolism (VTE), which is the third leading cause of CVD, has a very high incidence rate in Indian Population. Data suggest that thromboembolic disorders are due to multiple genetic and environmental variables and hence considered as a complex multifactorial trait. High Density Lipoprotein (HDL) has attracted a great deal of interest in recent years because of its implications in the prevention of various CVD. Various data suggests the relation between HDL and the expression of coagulation/fibrinolytic factors among the patients of CVD. Protein content of HDL is largely responsible for antioxidant mechanism by metabolizing lipid hydro peroxides and preventing their accumulation. Association of venous thrombosis and dyslipidemia has been investigated in several clinical studies, but results are inconsistent. Therefore, we sought to identify the role of HDL in pathophysiology of VTE in both human and animal studies.

Methodology

DVT was detected in male patients using color Doppler followed by D‐Dimer and Prothrombin Fragment 1+2 (PF1+2) levels to confirm thrombus formation. HDL associated proteins, endothelial adhesion molecules, thrombotic molecules, inflammatory molecules and oxidized lipoprotein levels were measured. For animal study, a complete stasis animal model was standardized to generate thrombus formation in the SD rats. Thrombus length/weight was measured along with D‐Dimer & PF 1+2 levels. HDL was isolated from plasma and was used in kinetic reaction of LDL oxidation. Progression of LDL oxidation was measured through DCFH‐method. All experimental procedures were performed in accordance to ethical guidelines.

Major Findings

A well written consent was taken from all the participants before conducting human study. High levels of D‐Dimer and PF 1+2 in DVT patients as well as IVC ligated group confirmed thrombosis. HDL associated molecules were found to be significantly lower, whereas adhesion molecules, inflammatory molecules, and thrombotic molecules were significantly higher in both DVT patients and IVC ligated group. Oxidized lipoproteins and the lipooxygenase enzymes responsible for lipoprotein oxidation were found significantly higher. Isolated HDL used in LDL oxidation kinetics reaction found to be non‐functional in preventing LDL oxidation. P‐value of <0.05 was used as significance for all the tests.

Conclusion & Discussion

Low levels of HDL proteins along with high levels of adhesion molecules, thrombotic markers and inflammatory molecules indicate the suppression of HDL activity. High lipooxygenase enzymes and oxidized lipoprotein levels support the hypothesis of dysfunctional HDL. HDL isolated from the ligated group was unable to prevent the LDL oxidation which clarifies that HDL loses its functionality in case of VTE. Furthermore, finding of this study will also help in understanding the pathophysiology of VTE which might give an insight in prevention/early diagnosis of the disease.