Principles of Clinical and Engineering Integration in Hemocompatibility - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 16

pregnancy loss, and various other clinical manifestations in the presence of
antiphospholipid antibodies (aPL) [2, 13, 14]. This syndrome can also per-
turb the function of endothelial cells, which are important in forming a
confluent layer within the lumen of the stent in order to minimize in-stent
stenosis. Similar to other autoimmune diseases, the etiology of APS has
been suggested to occur from a combination of genetic and environmental
factors [2, 13, 14, 42-46].
One important interaction related to thrombosis is that of aPL with endothe-
lial cells (EC). It has been demonstrated that aPL antibodies active endothelial
cells in vitro as an enhanced expression of adhesion molecules on human
umbilical vein endothelial cells along with enhanced monocyte adherence to
ECs in vitro. The adhesion molecules that have been demonstrated to show
increased expression include intercellular cell-adhesion molecule-1 (ICAM-1),
vascular cell adhesion molecule-1 (VCAM-1), and (E-selectin) [14, 42-45].
The perturbance of ECs in APS has been demonstrated in a clinical study
by Cugno et al. This study assessed the plasma levels of soluble adhesion
molecules (s-ICAM-1, s-VCAM-1, s-E-selectin), soluble thrombomodulin
(sTM), von Willebrand factor (vWF), and tissue plasminogen activator (tPA)
using solid-phase assays in 40 selected APS patients as well as 40 healthy
subjects matched accordingly by age and sex. Circulating endothelial cells
by flow cytometry and brachial artery flow-mediated vasodilation were also
evaluated. Their results indicated no noteworthy difference in plasma levels
of sTM, s-E-selectin, and s-VCAM-1 between the APS group and controls dif-
fer. However, a significant increase in s-ICAM-1 (P = 0.029), t-PA (P = 0.003),
and vWF titres (P = 0.002) was observed along with significantly higher lev-
els of circulating mature endothelial cells in patients (P = 0.05), which were
decreased when vitamin K antagonists and antiplatelet treatments were
administered to the APS patients group. In addition, it was demonstrated
that mean brachial artery flow-mediated vasodilation responses were sig-
nificantly impaired compared with those of healthy subjects (P = 0.0001) [42].
It is evident that the function of ECs can be impaired in APS. Much can be
learned about ECs in the APS milieu [14, 42, 43]. Enhanced characterization
of ECs in a variety of clinical settings may lead to a better understanding of
their role and variability in these settings. This knowledge may be re-applied
to attempt to improve surface modification in biomaterials, particularly in
cardiac stents, in order to better assist ECs to form a confluent layer within
cardiac stents to minimize in-stent thrombosis [1]. That is, more potential
targets may be identified for enhanced surface modification of biomateri-
als [1,8]. That may assist in developing a biomaterial accessible for a larger
patient population that would otherwise not be able benefit from biomateri-
als implanted in their bodies [1].
Since autoimmune states may develop at different ages, it is important
to know of their existence and the hypercoagulability potential that may
occur in autoimmunity such as APS. For example, a patient with APS
implanted with a biomedical device with a specific biomaterial may be