Molecular and cellular pathogenesis of endothelial lining in atrial fibrillation
Authors: Shetye Prasad , Dungan Gabriel , Syed Mushabbar , Hoppensteadt Debra , Siddiqui Fakiha , Laddu Atul , Fareed Jawed 
Published: May 2022

Introduction

Atrial Fibrillation (AF) is a cardiac arrhythmia that is caused by a miscoordination between the heart’s upper and lower chambers. von Willebrand Factor (vWF) is a glycoprotein that aids the formation of blood clots by helping platelets adhere to the blood vessels and to one another. Once a blood clot begins to break down, it releases a protein fragment known as D‐Dimer. Due to the nature of its production, D‐Dimer levels can often be used as an indicator for the presence of a blood clot in the circulatory system. Interleukin‐6 (IL‐6) is a cytokine that helps regulate immune response. It is produced by monocytes and macrophages in response to an infection or a tissue injury.

Purpose

The aim of this research was to analyze how levels of biomarkers of inflammation and thrombosis vary between AF patients and a normal human plasma group (NHP).

Hypothesis

Biomarkers of inflammation and thrombosis are present at higher levels in AF patients when compared to an NHP group.

Materials and Methods

The AF samples (n=53) were collected following the IRB protocols at Loyola University Medical Center and Loyola Heart & Vascular clinics, while the NHP group blood samples (n=48) were obtained from a centralized blood bank known as George King Biomedical (Overland Park, Kansas). vWF, D‐Dimer, and IL‐6 levels were measured in both the AF group and the NHP using commercially available sandwich ELISA kits.

Statistical Analysis

The biomarker levels were analyzed using PRISM GraphPad, IBM Statistical Package for Social Sciences (SPSS), and Microsoft Excel for important statistical characteristics, including mean, median, mode, standard error of the mean (SEM), standard deviation, minimum, maximum, and interquartile range. In addition, tests for normal distribution, quartile analysis, unpaired t‐tests, skewness, correlation analysis, and Mann‐Whitney tests were conducted. Lastly, the data was broken down into every tenth percentile to assess the distribution of the data.

Results

The data was organized using the following format: Mean ± SEM. When all the biomarkers were compared, there was no significant correlation between the three (all correlations were positive with r‐values below 0.2); however, they all showed an upregulation in the AF group when compared to the NHP group. For vWF, there was a 6663.785% increase in the AF group (AF 4796.200 ± 286.155 vs. NHP 70.910 ± 7.268). For D‐Dimer there was a 386.549% increase in the AF group (AF 913.379 ± 125.634 vs. NHP 187.726 ± 31.320). Lastly, for IL‐6 there was a 253.002% increase in the AF group (AF 4.409 ± 1.125 vs. NHP 1.249 ± 0.178). Furthermore, when the statistical significances between the biomarkers and the NHP group were analyzed, it was found that all three data groups held a p‐value less than 0.05 (<0.001 for vWF, <0.001 for D‐Dimer, and 0.0087 for IL‐6), deeming the data statistically significant and thus the null hypothesis is rejected for all three data sets.

Conclusion

The above research supports the hypothesis that there will be an upregulation in biomarkers of inflammation and thrombosis (vWF, D‐Dimer, IL‐6) in AF patients.