Biocompatibility of cardiovascular devices - Biomaterials and Devices for the Circulatory System - page 59

account the relative roles of these subpopulations of SMCs over the course
of the pathogenetic process. While the utilization of stents after angio-
plasty can serve to minimize the inward remodeling associated with this
injury response, these devices are still prone to the formation of restenotic
myointimal hyperplastic lesions. Thus a signifi cant factor in the biocompat-
ibility of any implanted cardiovascular device is its ability to minimize this
injury response.
It has been shown that ECM proteins associated with normal vessel
anatomy such as basement membrane proteins like laminins and collagen
Type IV tend to induce a quiescent 'contractile' phenotype while ECM
proteins associated with healing/injury response like fi bronectin, vitronec-
tin, some forms of collagen type I, fi brin, fi brinogen and others tend to lead
to a non-differentiated, 'synthetic' phenotype (Hedin et al. , 1988, 1999, 2004;
Thyberg and Hultgardh-Nilsson, 1994; Koyama et al. , 1996; Thyberg et al. ,
1997; Thyberg, 1998; Hirose et al. , 1999; Raines et al. , 2000; Jacob et al. ,
2001; Beqaj et al. , 2002; Kingsley et al. , 2002; Stegemann and Nerem, 2003;
Stegemann et al. , 2005). This is important, as signifi cant alterations in the
ECM on the surface of cardiovascular devices occur not only in the time
period immediately following implantation as protein adsorption and for-
mation of the fi brin coagulum occurs, but also throughout the pathogenic
injury response. In the vasculature, SMCs located towards the intimal
surface of the vessel are immediately surrounded by a relative decrease in
laminins and collagen Type IV as the basement membrane is denuded after
arterial injury. Subsequent deposition of clotting cascade proteins such as
fi brin and fi brinogen, can further promote the shift towards a 'synthetic'
phenotype in these cells, and the later deposition of the healing proteins
such as fi bronectin by SMCs and other cells can further promote the syn-
thetic response (Bendeck et al. , 1996). In vivo studies have demonstrated
that the conversion of SMCs within a myointimal lesion back to a 'contrac-
tile' phenotype is closely associated with the reappearance of laminin sur-
rounding these cells (Thyberg et al. , 1997; Thyberg, 1998).
How SMCs located deeper in the arterial media may be affected by the
early changes in ECM redistribution is unclear, as they are not in direct
contact with the immediate area of intraluminal injury; however, cell-cell
signaling from SMCs near the lumen or apoptotic SMCs in the media,
or paracrine interactions among the cells may be possible explanations.
Also, evidence that a signifi cant fraction of SMCs in myointimal lesions
may be non-proliferative, migratory cells from the arterial media highlights
the complicated injury response arising from the behavior of arterial SMC
subpopulations which demonstrate heterogeneous phenotypic characteris-
tics (Clowes and Schwartz, 1985; Bochaton-Piallat et al. , 1996; Regan et al. ,
2000; Christen et al. , 2001). Additionally, biomaterials themselves can affect
ECM proteins deposited by infi ltrating cells which can in turn modulate

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