Anti-Inflammatory Effect of Gallic Acid-Eluting Stent in a Porcine Coronary Restenosis Model

Abstract

Background: Gallic acid (3,4,5-trihydroxybenzoic acid) is a natural polyphenol and strong natural antioxidant found abundantly in red wine and green tea. The aim of this study was to examine the anti-inflammatory effect of a novel gallic acid-eluting stent in a porcine coronary restenosis model.

Methods: Fifteen pigs were randomized into three groups; in which a total of 30 coronary arteries (10 in each group) were implanted with gallic acid-eluting stents (GESs, n = 10), gallic acid and sirolimus-eluting stents (GSESs, n = 10), or sirolimus-eluting stents (SESs, n = 10). Histopathologic analysis was performed 28 days after stenting.

Results: There were no significant differences in injury score and fibrin score among the groups, however there were significant differences in the internal elastic lamina (4.0 ± 0.83 mm² in GES vs. 3.0 ± 0.53 mm² in GSES vs. 4.6 ± 1.43 mm² in SES, p < 0.0001), lumen area (2.3 ± 0.49 mm² in GES vs. 1.9 ± 0.67 mm² in GSES vs. 2.9 ± 0.56 mm² in SES, p < 0.0001), neointimal area (1.7 ± 0.63 mm² in GES vs. 1.1 ± 0.28 mm² in GSES vs. 1.7 ± 1.17 mm² in SES, p < 0.05), and percent area of stenosis (42.4% ± 9.22% in GES vs. 38.2% ± 12.77% in GSES vs. 33.9% ± 15.64% in SES, p < 0.05). The inflammation score was significantly lower in the GES and GSES groups compared to that in the SES group [1.0 (range: 1.0 to 2.0) in GES vs. 1.0 (range: 1.0 to 1.0) in GSES vs. 1.5 (range: 1.0 to 3.0) in SES, p < 0.05].

Conclusions: The GES group had a greater percent area of stenosis than the SES group. Although gallic acid in the GES and GSES groups did not show a synergistic effect in suppressing neointimal hyperplasia, it resulted in greater inhibition of the inflammatory reaction in the porcine coronary restenosis model than in the SES group.

Keywords: Inflammation; Percutaneous coronary intervention; Restenosis; Stent.

Figure 1

Schematic illustration of the GES, GSES, and SES. GES, gallic acid-eluting stent; GSES, gallic acid- and sirolimus-eluting stent; SES, sirolimus-eluting stent.

Figure 2

Scanning electron microscopy images (magnitude, ×50 and ×300) of the GES (A and A-1), GSES (B, B-1, and B-2), and SES (C, C-1, and C-2). GES, gallic acid-eluting stent; GSES, gallic acid and sirolimus-eluting stent; SES, sirolimus-eluting stent.

Figure 3

In vitro release kinetics of gallic acid (square dot) and sirolimus (round dot) on a stent over time.

Figure 4

Representative images of hematoxylin and eosin staining at 4 weeks after stenting. Specimens of implanted GES (A, ×20), GSES (B, ×20), and SES (C, ×20). Carstairs’ fibrin stain (magnitude, ×20) of fibrin infiltration in implanted GES (A-1, ×20), GSES (B-1, ×20), and SES (C-1, ×20). GES, gallic acid-eluting stent; GSES, gallic acid and sirolimus-eluting stent; SES, sirolimus-eluting stent.

Figure 5

Injury score (A), percent area of stenosis (B), fibrin score (C), and inflammation score (D) of GES, GSES, and SES. A, C, and D are expressed as the median (interquartile range). GES, gallic acid-eluting stent; GSES, gallic acid and sirolimus-eluting stent; SES, sirolimus-eluting stent.

Figure 6

Micro-CT analysis and representative images of in-stent restenosis of GES, GSES, and SES. GES, gallic acid-eluting stent; GSES, gallic acid and sirolimus-eluting stent; SES, sirolimus-eluting stent.