Collagen Remodeling Proteins, Inflammatory Biomarkers and FABP Regulation in Understanding the Pathogenesis of Atrial Fibrillation

Abstract

IntroductionAtrial Fibrillation (AF) is the most common sustained form of cardiac arrythmia across the world with around 3 million active cases. Atrial fibrosis is the process by which collagen is deposited within the atria. Atrial fibrosis is correlated with AF. PINP and PICP, the two collagen remodeling proteins focused on in this study, are procollagen type I remodeling proteins and effective biomarkers of collagen deposition and bone formation. PINP exhibits diurnal variation with higher values occurring at night resulting in variance within the data set for PINP in AF patients. Long chain fatty acids (LCFAs), in excess, can lead to lipotoxicity which increases the risk of a potential arrythmia. Fatty Acid Binding Proteins (FABPs) bind to LCFAs to create a lower level of these fatty acid chains in the cytoplasm. Increased LCFAs has a direct correlation with increased FABPs which can ultimately increase the risk of arrythmia.PurposeThe purpose of this study was to analyze levels of collagen remodeling proteins, specifically PINP and PICP, and L‐FABP in an AF cohort to determine whether they can serve as viable biomarkers in the management and diagnosis of AF.HypothesisIt is expected that there will be an upregulation of collagen remodeling proteins, inflammatory biomarkers and FABP in AF patients compared to the NHP.Materials and MethodsThe study was conducted with a sample of 50 normal healthy human plasma and were tested for PINP, PICP, and FABP levels. These normal samples were purchased from George King Biomedical. The blood of the AF patients was collected following IRB protocol, centrifuged, and aliquoted at –80 degrees Celsius. AF plasma samples were analyzed using sandwich ELISA Kits. Results were statistically analyzed by using the IBM SPSS software and PRISM Graphpad.ResultsThe results were collected as mean ± SEM with a percent change of mean (%) to demonstrate upregulation. All three biomarkers PINP, PICP, and FABP demonstrated an upregulation, respectively, of (422.32 ± 43.78, 164.47%), (1.395902 ± 0.178727, 104.86%), and (13186.7517 ± 4256.96265, 157.75% with the outlier and 77.69% without outlier). All three biomarkers were statistically significant with p‐values of <0.0001, <0.01, and <0.0001 respectively for PINP, PICP, and FABP. There was a significant outlier in the FABP data at 295.778.86 pg/mL. This value created a skewness statistic of 7.502 which changed to 3.795 after the outlier was removed. There was a strong, positive correlation between the two collagen remodeling proteins, PICP and PINP, with an r‐value (correlation coefficient) value of 0.62.ConclusionThe results prove that increased structural remodeling, proven by higher levels of collagen remodeling proteins, can indicate AF. FABP had an evident upregulation in the AF patient, but the data was severely skewed right due to an outlier. Once the outlier was removed, the data still demonstrated an upregulation of 77.69%. Elevated levels of these biomarkers suggest that they can serve as surrogate endpoints in the management and diagnosis of AF.