EDITORIAL
The opinions expressed in this article are not necessarily those of the Editors of EuroIntervention or
of the European Association of Percutaneous Cardiovascular Interventions.
1626
EuroIntervention 2018;13: 1626-1628 DOI: 10.4244/EIJV13I14A262
© Europa Digital & Publishing 2018. All rights reserved.
*Corresponding author: Department of Cardiology, Dr. Wytemaweg 80, room Ee2393a, Erasmus MC Medical Center,
PO Box 2040, 3000 CA Rotterdam, the Netherlands. E-mail: h.vanbeusekom@erasmusmc.nl
The importance of large animal atherosclerosis models in
studying the response to polymers and drug-eluting stents
Heleen M.M. van Beusekom
1
*, PhD; Volkert van Steijn
2
, PhD; Anouchska S.A. Autar
1
, MD
1. Experimental Cardiology, Erasmus MC Rotterdam, Rotterdam, the Netherlands; 2. Chemical Engineering, Delft University of
Technology, Delft, the Netherlands
Polymeric materials have long been used in the vasculature
1,2
.
We know that both degradable and permanent polymers can elicit
intense inflammatory responses in the arterial wall, even if the
polymer is deemed inert
3
. Much knowledge has been obtained
from studies searching for suitable materials to create synthetic
vascular grafts. We have learned that catalysts, initiators, poly-
mer degradation products and contaminants could all elicit inflam-
matory responses, even when present in small amounts (parts per
million). Importantly, inert polymers could even elicit intense
inflammatory responses years after implantation, when disinte-
grating into small particulate matter
3
. More than 20 years ago,
a multicentre preclinical trial tested a number of polymers to study
their applicability for the vascular bed
4
. This study marked the
beginning of the era of drug-eluting stents (DES) and was a first
attempt to discover which polymers might be suitable as coatings
or replacements for metallic stents. DES studies have taught us
that the inflammatory and neointimal response is not necessarily
dictated by (degradation of) the polymer alone, but rather by the
balance between drug release and polymers, degradants and the
like
5
. We have learned that the irritant effects of polymers leading
to an increase in neointimal thickening could suddenly become
apparent. For instance, when drug levels to suppress proliferation
dive below the suppressant threshold concentration of the drug,
this could lead to neointimal catch-up
5
. How the extent of athero-
sclerosis alters the vascular response to polymeric stents and coat-
ings remains largely unknown.
What we do know is that atherosclerosis alters the vascular
response to stents with a clear relationship between plaque mass
and neointimal hyperplasia after stenting
6,7
. Unpublished data
from our group (Table 1) support this. In this study, Yucatan
miniswine were placed on a normal or a high cholesterol diet
6
,
and bare metal stents (BMS) were placed as guided by quan-
titative coronary angiography (QCA). At six-week follow-up,
animals were sacrificed and stents were processed for routine
histology
5
, as previously described. Data showed a 2-3x larger
neointimal thickness and area after stenting for animals on the