Korean Circ J.  2025 Jan;55(1):50-64. 10.4070/kcj.2024.0171.

The Effects of Nicotine on Re-endothelialization, Inflammation, and Neoatherosclerosis After Drug-Eluting Stent Implantation in a Porcine Model

• Oh S
• Kim JH
• Ahmad S
• Jin YJ
• Na MH
• Kim M
• Kim JH
• Park DS
• Hyun DY
• Cho KH
• Kim MC
• Sim DS
• Hong YJ
• Lee Sw
• Ahn Y
• Jeong MH

• KMID: 2564716
• DOI: http://doi.org/10.4070/kcj.2024.0171

Abstract

Background and Objectives
Cigarette smoking is a major risk factor for atherosclerosis. Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).
Methods
After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI.
Results
Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group.
Conclusions
Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.

Keyword

Coronary restenosis; Drug-eluting stents; Nicotine; Smoking; Swine

Figure

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  Figure 1 Flowchart of the animal experiment.CAG = coronary angiography; LAD = left anterior descending coronary artery; OCT = optical coherence tomography; QCA = quantitative coronary angiography; RCA = right coronary artery.

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  Figure 2 Representative images from sections-morphometric analysis at 8 weeks after stent implantation. (A-D) Nicotine group. (E-H) No-nicotine group. The nicotine group demonstrates higher fibrin deposition around the stent strut than the no-nicotine group (whitish arrows).H&E = hematoxylin and eosin.

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  Figure 3 The morphometric measurements of porcine coronary arteries at 8 weeks after stenting. Compared to the no-nicotine group, the nicotine group shows a significantly larger neointima area and significantly greater percent stenosis with higher fibrin and inflammation scores.IEL = internal elastic lamina.

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  Figure 4 Representative images of immunofluorescence of CD68. The nicotine group displays a higher number of CD68-positive reactive cells (whitish arrows) than the no-nicotine group.CD68 = cluster of differentiation 68; DAPI = 4′,6 diamidino-2-phenylindole.

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  Figure 5 Representative images of immunofluorescence of α-SMA. The nicotine group displays a higher number of α-SMA-positive reactive cells than the no-nicotine group.α-SMA = alpha-smooth muscle actin; DAPI = 4′,6 diamidino-2-phenylindole.

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  Figure 6 Representative images of immunofluorescence of CD31. CD31 expression is lower in the nicotine group than in the no-nicotine group (whitish arrows).CD31 = cluster of differentiation 31; DAPI = 4′,6 diamidino-2-phenylindole.

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