In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia

Abstract

Objectives: We examined the relative contributions of inflammation and arterial injury to neointimal formation in a porcine coronary overstretch restenosis model.

Background: Previous studies established that stents cause neointimal proliferation proportional to injury. Although inflammation has been postulated to be a major contributor to restenosis after angioplasty, there is a paucity of data on the relation between inflammation and subsequent neointimal formation.

Methods: Twenty-one pigs underwent balloon injury followed by implantation of oversized, tubular, slotted stents (stent/artery ratio 1.2:1) in the left anterior descending coronary artery. Morphometric analysis of the extent of injury (graded as injury score 0 to 3) and inflammation (graded as inflammation score 0 to 3) 1 month later was assessed and correlated with neointimal formation.

Results: An inflammatory reaction was observed in 20 of 21 pigs, and significant positive correlations were found between the degree of arterial injury and the extent of the inflammatory reaction (r = 0.80, p < 0.01) and between the extent of inflammatory reaction and the neointimal thickness (r = 0.75, p < 0.01), neointimal area (r = 0.53, p = 0.01) and percent area stenosis (r = 0.66, p < 0.01) within the stents. Importantly, there were areas with inflammation only in the absence of injury, and vice versa, that were also associated with neointimal hyperplasia.

Conclusions: These data suggest that the inflammatory reaction plays an equally important role as arterial injury in neointimal formation after coronary stenting, and that anti-inflammatory approaches may be of value to reduce in-stent restenosis.