| Autor: |
Morris TA, Marsh JJ, Chiles PG, Auger WR, Fedullo PF, Woods VL Jr, Morris, Timothy A, Marsh, James J, Chiles, Peter G, Auger, William R, Fedullo, Peter F, Woods, Virgil L Jr |
| Zdroj: |
American Journal of Respiratory & Critical Care Medicine; 2006, Vol. 173 Issue 11, p1270-1275, 6p |
| Abstrakt: |
Rationale: 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.Objective: Determine whether fibrin from patients is more resistant to plasmin-mediated lysis than fibrin from healthy control subjects.Methods: 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.Measurements and Main Results: 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).Conclusions: The relative resistance of patient fibrin to plasmin-mediated lysis may be due to alterations in fibrin(ogen) structure affecting accessibility to plasmin cleavage sites. The persistence of structural motifs of fibrin, such as the beta-chain N-terminus, within the pulmonary vasculature could promote the transition from acute thromboemboli into chronic obstructive vascular scars. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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