Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 557

the LDLR-related protein (LRP) of the low-density lipoprotein receptor (LDLR)
family. It binds numerous other ligands, such as matrix proteins as well as
certain apolipoprotein E- and lipoprotein lipase-enriched lipoproteins, in addition
to peptidase-inhibitor complexes [ 1027 ].
Antithrombin 137 is a serine peptidase inhibitor (serpin-C1) that degrades
thrombin and coagulation factor-Xa, -XIIa, and -XIa. Its action is enhanced
by heparan sulfate proteoglycans and heparin. This glycoprotein is produced
by the liver. Antithrombin- α is the dominant plasmatic form of antithrombin;

β -antithrombin is a minor type.

Tissue factor pathway inhibitor inhibits coagulation factor-VIIa-mediated
activation of coagulation factor-IX and -X. Synthesis of TFPI occurs in the vascular
endothelium (which also expresses the tissue factor).
Serotonin inhibits platelet release of ADP messenger. Degradation products of
prostaglandin-E1 and fibrin preclude platelet material release. Furthermore, fibrin
degradation products also impede platelet aggregation.
Serpin-D1 138 inhibits thrombin (FIIa). This minor antithrombin serves as a
cofactor for heparin and dermatan sulfate proteoglycans. It indeed rapidly inhibits
thrombin in the presence of dermatan sulfate proteoglycans or heparin.
The relative abundance of various blood cell types within the fibrin clot depends
on the local hemodynamic stress field. The lower the shear, the higher the number of
erythrocytes in the fibrin network. Platelets aggregate at sites of blood vessel wall
injury and then serve as a surface for coagulation. They set the final structure of
fibrin. Afterward, thrombocytes influence fibrinolysis via their proteins and phos-
pholipids that modulate plasmin activity. Leukocytes that form mixed aggregates
with platelets affect clot structure [ 1008 ]. Platelets actually interact with and capture
neutrophils via P-selectins and integrins.
Platelets also secrete neutrophil and endothelial activators that generate
production of inflammatory cytokines and release of neutrophil granule content
with serine peptidases (elastase, cathepsin-G, and peptidase-3) and matrix
metallopeptidases (MMP8 is stored in specific granules and MMP2 and MMP9
in small-storage gelatinase granules). Platelets secrete matrix metallopeptidases,
such as MMP1, MMP2, and MMP9.
Upon activation, secreted leukocyte peptidases enhance von Willebrand factor-
dependent platelet adhesion. Neutrophils can also bind to von Willebrand factor.
Red blood cells entrapped in clot influence hemostasis by secreting procoag-
ulant substances and contributing to the phospholipid surface for assembly of

137 A.k.a. antithrombin-3 (AT3). Antithrombin-1 refers to the absorption of thrombin onto a fibrin
gel. Antithrombin-2 is a cofactor in plasma that, with heparin, interferes with the interaction of
thrombin and fibrinogen. Antithrombin-4 is an antithrombin that is activated during and shortly
after blood coagulation.
138 A.k.a. heparin cofactor-2 and peptidase inhibitor leuserpin-2.