Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 562

stresses. Shear stress-dependent platelet transport and activation, the extrinsic path-
way of coagulation leading to a viscoelastic clot and fibrinolysis 146 are represented
by a set of coupled advection-diffusion-reaction equations, assuming a uniform
distribution of platelets, reactants, and regulators in a shear-thinning viscoelastic
blood for a given wall flux of stimulating agents.

9.9 Effects of High-Density Lipoproteins on Endothelium

High-density lipoproteins decrease the lipid peroxidation of LDL, due to the
presence of paraoxonase-1 (PON1) [ 1042 ]. Furthermore, HDLs influence several
functions of the vascular endothelium [ 1043 ].
High-density lipoprotein acts on the vascular tone via vasoactive substances re-
leased by endothelium. It activates constitutive NOS3 and inducible COx2, releasing
NO and PGi2 agents. It triggers MAPK signaling via scavenger receptor ScaRb1 on
endothelial cells. In vivo, the plasma concentration of HDLc is used as a predictor
of NO-dependent vasodilation and correlates with the plasma concentration of the
stable PGi2 metabolite 6-keto PGf1

. Moreover, HDL may inhibit ET1 secretion.
High-density lipoprotein intervenes in inflammation. It downregulates TNF

α

,
and consequently decreases the synthesis of cell adhesion molecules, reducing
leukocyte recruitment and extravasation. It reduces the production of platelet-
activating factor. Furthermore, PAF is also degraded by HDL-bound enzymes,
platelet-activating factor acetylhydrolase (PAFAH), LCAT, and paraoxonase. High-
density lipoprotein then prevents PAF-induced adhesion of leukocytes to the
endothelium. However, HDL may lose its anti-inflammatory properties during
inflammation, part of apoA1, apoA2, paraoxonase, and PAFAH being removed.
High-density lipoprotein is involved in coagulation. It enhances the synthesis
of antithrombotic NO and PGI2 agents. It limits PAF level. It may also repress
the production of von Willebrand factor. It binds to tissue factor pathway inhibitor,
hampering the extrinsic coagulation pathway. It enhances the anticoagulant activity
of protein-C and -S.
High-density lipoprotein stimulates the proliferation of endothelial cells, in
association with phospholipase-C and intracellular calcium. It protects cultured
endothelial cells from TNF

α

-induced apoptosis, inhibiting caspase-3. It suppresses
the mitochondrial pathway of apoptosis, activating PKB kinase.

α

146 Fibrinolysis occurs when fibrin concentration decays below a given threshold or the local shear
stress reaches a critical value that depends on concentrations of platelets and fibrin.