Principles of Clinical and Engineering Integration in Hemocompatibility - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 10

CardioGene Study
A large study called the CardioGene Study was created under the auspices
of the National Heart, Lung and Blood Institute to further understand the
factors involved in in-stent restenosis (ISR) in bare mental stents (BMS) for
the treatment of coronary artery disease. The overall goal of the study was
to understand the genetic determinants of the responses to vascular injury
that result in the development of restenosis in some patients but not in oth-
ers. In this study, global-gene and protein-expression profiling were used to
define the molecular phenotypes of patients. Well-defined clinical pheno-
types were paired with genomic data to define analyses in order to deter-
mine blood gene and protein expression in patients with ISR, investigate the
genetic basis of ISR, develop a predictive gene and protein biomarkers data-
base, and identify new targets for treatment. Interestingly, the implications
of such a study for biomaterials science can include the following:
• Identifying which patients would less likely beneit from treatment
despite a relatively inert biomaterial.
• Identifying new targets to be used for surface modiication.
• Providing alternative solutions that emphasize thrombogenic prop-
erties of predisposed patients carrying polymorphisms—which may
also be helpful for patients without these types of polymorphisms.
Such databases can have enormous potential for improving surface modi-
fication of biomaterials in a variety of settings [8].
One potential application of genetic polymorphism testing has been
found in the use of drug-eluting stents (DES). DESs, while reducing in-stent
restenosis after percutaneous coronary intervention (PCI), have been associ-
ated with late stent thrombosis. No accurate method of predicting in-stent
restenosis has been found; it should be noted that several risk factors for
atherosclerosis do overlap with those for in-stent restenosis. In addition,
atherosclerosis candidate genes have been investigated for their possible
association with in-stent restenosis [2, 16-24].
Polymorphisms in Inflammation and Proliferation
Effects on In-Stent Stenosis
Polymorphisms related to proliferation and inflammation may contribute to
in-stent stenosis. Inflammatory activities as well as proliferation of particular
cells such as smooth muscle cells can contribute to in-stent stenosis. These
effects are related to vascular remodeling after procedures, such as percuta-
neous coronary stent implantation, that frequently lead to stenosis. One par-
ticular enzyme, heme oxygenase 1 (HO-1), is involved in the generation of the
endogenous antioxidant bilirubin and carbon monoxide, both of which have
anti-inflammatory and antiproliferative effects. Gulesserian et al. showed