title: Iron-induced fibrin in cardiovascular disease.
abstract: Accumulating evidence within the last two decades indicates the association between cardiovascular disease (CVD) and chronic inflammatory state. Under normal conditions fibrin clots are gradually degraded by the fibrinolytic enzyme system, so no permanent insoluble deposits remain in the circulation. However, fibrinolytic therapy in coronary and cerebral thrombosis is ineffective unless it is installed within 3-5 hours of the onset. We have shown that trivalent iron (FeIII) initiates a hydroxyl radical-catalyzed conversion of fibrinogen into a fibrin-like polymer (parafibrin) that is remarkably resistant to the proteolytic dissolution and thus promotes its intravascular deposition. Here we suggest that the persistent presence of proteolysis-resistant fibrin clots causes chronic inflammation. We study the effects of certain amphiphilic substances on the iron- and thrombin-induced fibrinogen polymerization visualized using scanning electron microscopy. We argue that the culprit is an excessive accumulation of free iron in blood, known to be associated with CVD. The only way to prevent iron overload is by supplementation with iron chelating agents. However, administration of free radical scavengers as effective protection against persistent presence of fibrin-like deposits should also be investigated to contribute to the prevention of cardiovascular and other degenerative diseases.
authors.affiliation: Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Lipinski
authors.forename: Etheresia
authors.initials: E
authors.lastname: Pretorius
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000188:drug therapy; D005337:Fibrin / Q000096:biosynthesis*; D016166:Free Radical Scavengers / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007501:Iron / Q000097:blood*; D015912:Thrombolytic Therapy / Q000379:methods
chemical_list: D016166:Free Radical Scavengers; D005337:Fibrin; D007501:Iron