Upregulation of Inflammatory Biomarkers in Pulmonary Embolism as Studied by a Biochip‐Array Profiling Approach
Authors: Bontekoe Emily , Brailovsky Eugene , Hoppensteadt Debra , Siddiqui Fakiha , Farooqui Ambar , Iqbal Omer , Fareed Jawed , Darki Amir 
Published: April 2020

Introduction

The incidence of Pulmonary embolism (PE) is estimated to be 60 to 70 per 100,000, and that of venous thrombosis is 125 per 100,000 cases, in the general population. The pathophysiology of PE is complex including both the systemic and localized involvement. Hemostatic activation, inflammatory processes, and cellular dysfunction, along with hemodynamic aberrations contribute to the progression and outcome of PE. Inflammatory mediators such as the interleukins, oxidative stress molecules, and other cellular products contribute to the overall pathophysiology. Biochip‐array technology using protein chips provides an integrated high throughput approach in analyzing blood plasma samples for multiple parameters. The purpose of this study is to profile biomarkers of inflammatory processes in the baseline blood samples collected from patients diagnosed with PE.

Materials and Methods

Blood plasma samples from patients with clinically confirmed diagnosis (n=119) were collected in citrated tubes at Loyola University Medical Center and an affiliated hospital under an IRB approved protocol. These samples were processed for platelet‐poor plasma, which was banked at −80 C. These samples were retrospectively analyzed for such biomarkers as IL2, IL4, IL6, IL8, IL10, vascular endothelial growth factor (VEGF), gamma interferon (IFNG), tumor necrosis factor a (TNFa), IL1a, IL1b, monocyte chemotactic protein (MCP1), and epidermal growth factor (EGF). The Randox Signature System (Crumlin, North Ireland, UK) was used for profiling these markers. The control samples represented a pool prepared from healthy normal individuals for the comparison of each of these biomarkers. The PE patient results were compiled as group mean ±/‐ SD and fold change was calculated.

Results

In comparison to the normal controls, marked increase in IL6 (53 fold), IL8 (8 fold), IL10 (6 fold), VEGF (0.9 fold), TNFa (0.9 fold), IL1a (0.5 fold), IL1b (0.7 fold), MCP1 (0.5 fold), EGF (4 fold). In contrast, IL2 (14%), IL4 (3%), and IFNG (25%) showed a decrease in the circulating levels in PE patients in comparison to the controls. Marked variations in the circulating levels of such biomarkers as IL6, IL8, IL 10 and VEGF were evident by a large scatter in the data. No correlation between the individual mediators profiled in this study was noted.

Discussion

These results demonstrate that the pathophysiology of PE is associated with the activation of inflammatory processes resulting in the upregulation of various biomarkers. IL6, IL8, and IL10 showed the most significant increase, reflecting inflammatory processes, along with the other biomarkers. Randox biochip‐array biotechnology provides an integrated approach utilizing a small amount of sample for a complete profile for the inflammatory cytokines included in this study. These results clearly suggest that aside the activation of clotting processes, inflammation plays an important role in the overall pathogenesis of PE.