Biomedical Engineering Reference
In-Depth Information
Ang II
LOX-Transcription
Fig. 4
NF-kB induced inl ammation and adhesion molecule expression in AF. Atrial i brillation
(AF) leads to increased ROS-production followed by
IκB phosphorylation. h is unmasks the
p50/p65 NF-kB components and their nuclear localization signal. At er translocation to the cell
nucleus they account for increased expression of adhesion molecules and lectin-like oxidized low-
density lipoprotein receptor receptor (LOX-1), which itself is a stimulus for increased expression
of the adhesion molecules ICAM-1, VCAM-1 and P-selectin. Angiotensin receptor blockers
(ARB), calcium antagonist verapamil, NADPH oxidase inhibitor apocynin and NF-kB inhibitor
resveratrol can reduce adhesion molecule production on various stages of the NF-kB signaling
pathway .
molecules could be an important link between the initiation of pro-inl ammatory
and prothrombogenic mechanisms responsible for atrial thrombus formation
(Gawaz
et al.
1998, Hammwöhner
et al.
2007b). As demonstrated in Fig. 5, AF-
induced thromboemboli are very leukocyte rich, showing the close link between
coagulation and inl ammation in atrial thrombus formation.
In AF, interaction between inl ammatory cells and platelets is increased
by enhanced platelet P-selectin expression binding to its endothelial receptor
P-selectin glycoprotein ligand 1 (PSGL-1)
(Fig. 6)
(Goette
et al.
2000a). Kamiyama
(1998) was also able to show increased P-selectin expression on the endothelial
surface layer, which was accompanied by positively ICAM-1 stained adherent
leukocytes in an AF-rabbit model. Endothelial adhesion molecule expression
was also proven to be AngII dependent and declined at er administration of an
