Summary
Restenosis following successful percutaneous coronary revascularization continues
to represent a major problem limiting the clinical efficacy of this procedure. The
underlying mechanisms of restenosis are comprised of a combination of effects from
vessel recoil, negative vascular remodeling, thrombus formation and neointimal hyperplasia.
Indeed, there are important interactions among all of these mechanisms. For example,
neointimal hyperplasia is stimulated by growth factors, which are released by local
thrombi and the injured arterial segment itself, and act to enhance the expression
of other growth-regulating proteins, in particular “second messengers“, proto-oncogenes
and other cell cycle controlling proteins. This results in an inflammatory and myofibroproliferative
response, which may worsen vessel narrowing caused by recoil and result in the formation
of a clinically significant restenotic lesion.
A multitude of pharmacologic trials have been conducted in an attempt to prevent restenosis,
but most have demonstrated little benefit. Studies in smaller numbers of patients
have suggested a potential benefit for several classes of agents, including: 1) the
antiproliferatives, angiopeptin, trapidil and tranilast; 2) selective elimination
or alteration of proliferating cells; 3) enhancement of natural growth inhibitors;
and 4) signal transduction blockade or inhibition of the gene expression for various
growth-stimulating proteins. Finally, there have been advances in related areas, including
development of antithrombotic catheters, novel polymers, and more efficient methods
for transferring genes into the vessel wall. All of these offer the possibility of
delivering agents (drugs, genes, or antisense oligonucleotides) locally at the site
of intervention in a way that may optimize antiproliferative effects while minimizing
systemic effects – ultimately leading to a more specific inhibition of the restenosis
process.
Key words
Angioplasty - coronary artery disease - restenosis - thrombosis
