ABC | Volume 111, Nº2, August 2018

Original Article Persistent Inflammatory Activity in Blood Cells and Artery Tissue from Patients with Previous Bare Metal Stent Pedro Silvio Farsky, 1 Mario H. Hirata, 2 Renato Tambellini Arnoni, 1 Antonio Flavio Sanches Almeida, 1 Mario Issa, 1 Paula Helena Ortiz Lima, 1 Maria de Lourdes Higuchi, 3 Hui T Lin-Wang 2 Instituto Dante Pazzanese de Cardiologia, 1 São Paulo, SP - Brazil Laboratório de Investigação Molecular em Cardiologia, 2 Instituto Dante Pazzanese de Cardiologia, São Paulo, SP – Brazil Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 3 São Paulo, SP - Brazil Mailing Address: Pedro Silvio Farsky • Rua Alberto Faria, 248. Postal Code 05459-000, Alto de Pinheiros, São Paulo, SP – Brazil E-mail: pedro.farsky@gmail.com Manuscript received August 20, 2017, revised manuscript February 23, 2018, accepted February 23, 2018 DOI: 10.5935/abc.20180119 Abstract Background: Studies have pointed out a higher mortality after coronary artery bypass surgery (CABG) in patients with stent. Objective: To evaluate inflammatory markers in peripheral blood cells and in coronary artery tissue samples obtained during CABG in patients with stent compared to controls. Methods: The case series consisted of two groups, one with previous stent implantation (n = 41) and one control (n = 26). The expression of the LIGHT, IL-6, ICAM, VCAM, CD40, NFKB, TNF, IFNG genes was analyzed in peripheral blood cells collected preoperatively. The coronary artery was evaluated for: interleukin-6, ICAM, VCAM, CD40, NFKB, TNF-alpha and IFN-gamma by immunohistochemistry. A total of 176 tissue samples were grouped for analysis in: A1- arteries with stent (n = 38); A2- native arteries from patients with stent in another artery (n = 68); and A3- arteries without stent from controls undergoing routinely CABG surgery (n = 70). A significance level of 0.05 was adopted. Results: Patients with stent showed higher TNF (p = 0.03) and lower CD40 gene expression (p = 0.01) in peripheral blood cells than controls without stent. In coronary artery samples, the TNF-alpha protein staining was higher in the group A1, not only in the intima-media layer (5.16 ± 5.05 vs 1.90 ± 2.27; p = 0.02), but also in the adipose tissue (6.69 ± 3.87 vs 2.27 ± 4.00; p < 0.001). Furthermore, group A1 had a higher interleukin-6 protein staining in adipose tissue than group A3 (p = 0.04). Conclusion: We observed a persistently higher systemic TNF expression associated with exacerbated TNF-alpha and interleukin-6 local production in patients with stents. This finding may contribute to a worse clinical outcome. (Arq Bras Cardiol. 2018; 111(2):134-141) Keywords: Percutaneous Coronary Intervention; Blood Cells; Inflammation; Stents; Polymerase Chain Reaction; Immunohistochemistry; Tumor Necrosis Factor-alpha; Interleukin-6. Introduction Retrospective studies have suggested that coronary artery bypass grafting (CABG) surgery after percutaneous coronary intervention (PCI) can impair short and long-term outcomes. 1-7 Previous studies have demonstrated that PCI is associated with higher in-hospital mortality, despite the lower risk profile of PCI patients, 3 but there is no consensus in the literature. 8 An analysis of the MASS study 9 has shown that patients who underwent PCI treatment were more likely to develop progression in native coronary arteries, than those undergoing CABG or medical treatment. During PCI, a focal inflammatory reaction occurs with plaque rupture caused by stent implantation, but there are still controversies if this reaction persists in the long term. There is scarce information about a persistent systemic inflammatory reaction or tissue mediators in coronary artery after stent implantation, as well as about the comparison between coronary arteries with stent, coronary arteries without stent but with stent in another artery and controls patient. The CABG allows a unique opportunity to collect coronary artery specimen to evaluate local inflammatory reaction long after stent implantation. This study aims to evaluate inflammatory genes expression in peripheral blood cells and inflammatory protein localization in coronary artery tissue obtained during CABG from patients with and without previous stent implantation. It is worth mentioning that CABG represents a unique opportunity to obtain a tiny coronary artery tissue sample to evaluate local inflammatory in humans. Nowadays, patients who receive previous bare metal stent (BMS) implantation and need CABG surgery later represent a significant number of cardiology hospital patients, especially in developing countries. Our results can contribute to clarify the involvement of persistent local and systemic inflammation in the later phase of stent restenosis. 134