Serum Level of Fibrinogen Aα Chain Fragment Increases in Chronic Thromboembolic Pulmonary Hypertension

Background: The cause of chronic thromboembolic pulmonary hypertension is unknown and there is no specific circulating biomarker for its detection. The aim of the present study was to use proteomic analysis to detect serum biomarkers by evaluating the serum profiles of low-molecular-weight peptides using matrix-assisted laser desorption/ ionization time-of-flight/time-of-flight mass spectrometry in patients with chronic thromboembolic pulmonary hypertension. Methods and Results: Serum low-molecular-weight peptide profiling using the spectrophotometric technique was studied retrospectively in patients with chronic thromboembolic pulmonary hypertension and in controls matched for sex and age. The serum level of a 2989-Da peptide in the sera of patients was significantly higher compared to that of controls. Tandem mass spectrometry indicated that the peptide was a fragment of fibrinogen Aα chain (KMADEAGSEADHEGTHSTKRGHAKSRPV). The serum level of fibrinogen Aα chain fragment, measured using a heavy isotope internal standard, tended toward negative correlation with plasmin -α2-plasmin inhibitor complex (P=0.073) and had a positive correlation with thrombin - anti-thrombin complex (P=0.031). Conclusions: This fragment may be a potential diagnostic biomarker for chronic thromboembolic pulmonary hypertension.