Fibrin derived from patients with chronic thromboembolic pulmonary hypertension is resistant to lysis

American Journal of Respiratory and Critical Care Medicine
Timothy A MorrisVirgil L Woods

Abstract

Although acute pulmonary embolism is epidemiologically associated with chronic thromboembolic pulmonary hypertension, the factors responsible for resistance to thrombolysis and a shift toward vascular remodeling within the pulmonary arteries of patients with chronic thromboembolic pulmonary hypertension are unknown. Determine whether fibrin from patients is more resistant to plasmin-mediated lysis than fibrin from healthy control subjects. Fibrinogen purified from patients and control subjects was used to prepare fibrin clots, which were subsequently digested with plasmin for various periods of time. The degradation of the alpha-, beta-, and gamma-chains of fibrin and the appearance of peptide fragments over time were assessed by polyacrylamide gel electrophoresis and Western blotting. Densitometry of Coomassie-stained gels revealed significantly slower cleavage of all three polypeptide chains of fibrin from patients compared with control subjects (p < 0.05). In particular, release of N-terminal fragments from the beta-chain of fibrin, which promote cell signaling, cell migration, and angiogenesis, was retarded in patients compared with control subjects (p < 0.01). The relative resistance of patient fibrin to plasmin-mediated l...Continue Reading

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