Biomedical Engineering Reference
In-Depth Information
Recently, in
ex vivo
experiments using organotypic human atrial tissue cultures
and
in vivo
experiments, we found an increased atrial expression of VCAM-1
in patients with paroxysmal and persistent AF. Importantly, we were able to
demonstrate that the increased expression of atrial adhesion molecules occurs
within hours of rapid atrial pacing (Goette
et al.
2008a). h is may explain why
there was no dif erence in atrial VCAM-1 expression in patients with persistent
and paroxysmal AF. Of note, blockade of the AT1R by irbesartan or olmesartan
reduced adhesion molecule expression in atrial tissue during rapid pacing. h ese
i ndings support the assumption that therapy with AT1R blockers (ARB) may
ef ect atrial thrombus formation. Nevertheless, the clinical benei t of ARB therapy
in reducing thromboembolism in AF has still to be proven.
One important factor that may inl uence endocardial protein expression is let
ventricular failure causing cardiac pressure and volume overload. In our recent
study (Goette
et al.
2008a), we were also able to demonstrate an association
between let ventricular function and atrial VCAM expression using multivariable
analysis. However, hemodynamic alterations were absent in the
in vitro
system
or were constant in the
in vivo
experiments. h is demonstrates that AF itself can
induce alterations in VCAM expression. Nevertheless, heart failure is a known
risk factor for stroke in patients with AF. One explanation for this i nding might
be the impact of let ventricular dysfunction on atrial expression of VCAM-1.
Accordingly, concomitant diseases (e.g., heart failure, diabetes) and gender seem
to inl uence atrial VCAM-1 levels during AF, which may also explain persistently
elevated VCAM-1 levels in the systemic circulation at er successful cardioversion
of AF (Hammwöhner
et al.
2007b). Nevertheless, the contribution of diabetes
mellitus and heart failure per se on atrial VCAM-1 expression needs further
evaluation.
Importantly, we found quantitative dif erences in VCAM-1 expression in
the right and let atria as a response to AF. During rapid atrial pacing, adhesion
molecule levels increased more signii cantly in the let atrial tissue than in the right
atrium. h is may help to explain why thrombus formation is typically observed in
the let atrial appendage, whereas right atrial thrombus formation with consecutive
pulmonary embolism is a rare event in patients with AF. For our recent large series
of tissue micro-array analyses (Goette
et al.
2008a), only right atrial tissue samples
were available. However, the results of our animal experiments suggest that
analyses of let atrial tissue samples might have revealed even more pronounced
dif erences in endocardial VCAM expression.
VON WILLEBRANDT FACTOR
Of note, besides ICAM-1, VCAM-1, and P-selectin, no other adhesion
molecules (integrins, cadherins, lymphocyte homing receptors, molecules of the
immunoglobulin superfamily cell adhesion molecules (IgSF-CAMs), or other
