Matteo Becatti1, Rossella Marcucci1, Giulia Bruschi1, Niccolò Taddei1, Daniele Bani1, Anna Maria Gori1, Betti Giusti1, Gian Franco Gensini1, Rosanna Abbate1, Claudia Fiorillo2. 1. From the Department of Experimental and Clinical Biomedical Sciences (M.B., G.B., N.T., C.F.), Department of Clinical and Experimental Medicine, Thrombosis Centre (R.M., A.M.G., B.G., G.F.G., R.A.), and Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, Research Unit of Histology and Embryology (D.B.), University of Florence, Florence, Italy; and Don Carlo Gnocchi Foundation, Florence, Italy (A.M.G., G.F.G.). 2. From the Department of Experimental and Clinical Biomedical Sciences (M.B., G.B., N.T., C.F.), Department of Clinical and Experimental Medicine, Thrombosis Centre (R.M., A.M.G., B.G., G.F.G., R.A.), and Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, Research Unit of Histology and Embryology (D.B.), University of Florence, Florence, Italy; and Don Carlo Gnocchi Foundation, Florence, Italy (A.M.G., G.F.G.). claudia.fiorillo@unifi.it.
Abstract
OBJECTIVE: Among plasma proteins, fibrinogen represents a major target of oxidative modifications. In patients with post-acute myocardial infarction (6 months after the acute event), fibrinogen oxidation-induced carbonyls and fibrinogen function were estimated using in vitro and ex vivo approaches. Fibrinogen structural features and clot architecture were also explored. APPROACH AND RESULTS: In 39 patients with post-acute myocardial infarction and 28 age-, sex-, and risk factor-matched controls, oxidative stress markers (in plasma and in purified fibrinogen fractions), thrombin-catalyzed fibrin polymerization, and plasmin-induced fibrin lysis were estimated. Circular dichroism spectra of purified fibrinogen extracts, electron microscopy, and differential interference contrast microscopy analyses of fibrin clots were also performed. Marked signs of oxidative stress in plasma (P<0.01 versus controls) and, correspondingly, an increased extent of fibrinogen carbonylation (3.5-fold over control values; P<0.01 versus controls) were observed in patients. Furthermore, fibrinogen fractions purified from patients exhibited significantly reduced clotting ability and decreased susceptibility to plasmin-induced lysis (P<0.01 versus controls). Alterations in fibrinogen secondary structure, as suggested by circular dichroism spectroscopy, and in fibrin clot architecture, as analyzed by electron and differential interference contrast microscopy, were also identified. CONCLUSIONS: Here, we report for the first time that patients with post-acute myocardial infarction present with an overall imbalance in redox status and marked fibrinogen carbonylation associated with altered fibrinogen function, thus suggesting a role for carbonylation as a direct mechanism of fibrinogen function. The observed features occur along with modifications in protein structure and in clot architecture.
OBJECTIVE: Among plasma proteins, fibrinogen represents a major target of oxidative modifications. In patients with post-acute myocardial infarction (6 months after the acute event), fibrinogen oxidation-induced carbonyls and fibrinogen function were estimated using in vitro and ex vivo approaches. Fibrinogen structural features and clot architecture were also explored. APPROACH AND RESULTS: In 39 patients with post-acute myocardial infarction and 28 age-, sex-, and risk factor-matched controls, oxidative stress markers (in plasma and in purified fibrinogen fractions), thrombin-catalyzed fibrin polymerization, and plasmin-induced fibrin lysis were estimated. Circular dichroism spectra of purified fibrinogen extracts, electron microscopy, and differential interference contrast microscopy analyses of fibrin clots were also performed. Marked signs of oxidative stress in plasma (P<0.01 versus controls) and, correspondingly, an increased extent of fibrinogen carbonylation (3.5-fold over control values; P<0.01 versus controls) were observed in patients. Furthermore, fibrinogen fractions purified from patients exhibited significantly reduced clotting ability and decreased susceptibility to plasmin-induced lysis (P<0.01 versus controls). Alterations in fibrinogen secondary structure, as suggested by circular dichroism spectroscopy, and in fibrin clot architecture, as analyzed by electron and differential interference contrast microscopy, were also identified. CONCLUSIONS: Here, we report for the first time that patients with post-acute myocardial infarction present with an overall imbalance in redox status and marked fibrinogen carbonylation associated with altered fibrinogen function, thus suggesting a role for carbonylation as a direct mechanism of fibrinogen function. The observed features occur along with modifications in protein structure and in clot architecture.
Authors: A V Bychkova; A D Vasilyeva; A E Bugrova; M I Indeykina; A S Kononikhin; E N Nikolaev; M L Konstantinova; M A Rosenfeld Journal: Dokl Biochem Biophys Date: 2017-07-20 Impact factor: 0.788