Zinc Alters Fibrin Ultrastructure

Abstract

SummaryTurbidimetric studies indicate that Zn(II) accelerates fibrin gelation [decreases clotting time (CT)] and increases maximal fibrin clot turbidity. For any given level of fibrinogen (0.2-2.6 mg/ ml), the relative fibrin turbidity of thrombin-induced clots increases with Zn(II) in a concentration dependent manner. Zinc-associated turbidity increases are also observed in the presence of 2 mM Ca(II). With citrate, similar turbidity increases are observed, though at higher cation levels. Thus, turbidimetry indicates that the gel formed with Zn(II) is coarser, or has thicker fibre strands. SEM micrographs confirm that fibre thickness ranges from 260 Å to 2600 Å, when Zn(II) levels range from 0-50 uM. With citrate, TEM micrographs reveal amore than 20 x fold increase in fibre diameter (100 Å->2000 Å) with higher Zn(II) (<1 mM) levels. Based on a fibrin monomer cross-section of ~60 Å, the electron micrographs indicate that depending on the Zn(II) levels, fibrin strands are composed of between 2 to 40 monomeric fibrin molecules. Thus, at physiologically relevant levels, Zn(II) can drastically modulate fibrin ultrastructure.

Zinc-induced Alzheimer's Aβ1–40 Aggregation Is Mediated by Conformational Factors

“…Platelet zinc release modulates the propagation of the coagulation cascade through its action on protease activities, such as the effect of zinc at micromolar concentrations in se-lectively enhancing the inhibition of coagulation factor XIa by protease nexin-2/APP (51), probably through binding to the zinc-binding site on the amino terminus of APP (38). Zinc release also modulates the assembly of clotting structural elements such as fibrin in the vicinity of the activated platelet (47). In the current report we have found that zinc appears to mediate a reversible aggregation response from A␤, similar to the gelation response of fibrin incubated with low micromolar concentrations of zinc (47).…”

“…Zinc release also modulates the assembly of clotting structural elements such as fibrin in the vicinity of the activated platelet (47). In the current report we have found that zinc appears to mediate a reversible aggregation response from A␤, similar to the gelation response of fibrin incubated with low micromolar concentrations of zinc (47). A␤ could conceivably be recruited by high regional concentrations of zinc into the hemostatic plug or a reversible assembly that may play a role in maintaining tissue integrity in injury.…”

“…We hypothesize that the presence of A␤ precipitates in the brain in these conditions may reflect a physiological purpose. The zinc-mediated reversible precipitation of A␤ can be compared with the interaction of zinc with fibrin whose solubility state is dependent upon zinc for physiological purposes (47). A␤ is found in platelets (48) where it may colocalize with high concentrations (Ͼ300 M) of zinc as well as the APP (49), fibrinogen, and other coagulation factors (50) in the ␣-secretory granule.…”

Endotoxin enhances microvascular thrombosis in mouse cremaster venules via a TLR4-dependent, neutrophil-independent mechanism

“…Signs of endothelial injury were evident, including vacuole formation, but endothelial denudation was not detected. Fibrin, which has a distinct ultrastructural appearance (21,27), was not observed in the thrombi. There was no detectable difference in relative platelet degranulation between the two groups.…”

The simultaneous occurrence of both hypercoagulability and hypofibrinolysis in blood and serum during systemic inflammation, and the roles of iron and fibrin(ogen)

“…383, [403][404][405] healthy individuals. Thrombin with and without either phytic acid or thiourea (final concentrations 30 mM) was added to PRP (pH: 7.38 (physiological pH)).…”