Macromolecular approaches to prevent thrombosis and intimal hyperplasia following percutaneous coronary intervention

Abstract

Cardiovascular disease remains one of the largest contributors to death worldwide. Improvements in cardiovascular technology leading to the current generation of drug-eluting stents, bioresorbable stents, and drug-eluting balloons, coupled with advances in antirestenotic therapeutics developed by pharmaceutical community, have had a profound impact on quality of life and longevity. However, these procedures and devices contribute to both short- and long-term complications. Thus, room for improvement and development of new, alternative strategies exists. Two major approaches have been investigated to improve outcomes following percutaneous coronary intervention including perivascular delivery and luminal paving. For both approaches, polymers play a major role as controlled research vehicles, carriers for cells, and antithrombotic coatings. With improvements in catheter delivery devices and increases in our understanding of the biology of healthy and diseased vessels, the time is ripe for development of novel macromolecular coatings that can protect the vessel lumen following balloon angioplasty and promote healthy vascular healing.

Figure 1

Schematic representation of (A) a healthy vessel and (B–D) the progression of restenosis in an injured vessel following PCI (not to scale). (A) Blood vessels have three distinct layers, intima, media, and adventitia, which are separated by elastic lamina. In a normal vessel, the intima is comprised of a monolayer of ECs, while the media contains circumferentially aligned SMCs in a matrix of collagen. (B) After PCI, ECs are denuded from the wall exposing the underlying collagen matrix to which platelets can bind, activate and secrete growth factors. (C) Growth factors secreted from activated platelets recruit inflammatory cells to the site of injury and (D) stimulate SMC proliferation, migration, and ECM synthesis, ultimately resulting in intimal hyperplasia.