ABC | Volume 111, Nº4, Octuber 2018

Original Article Effects of Rosuvastatin on Apolipoprotein J in Balloon-Injured Carotid Artery in Rats Ning Yang, Bo Dong, Jinyu Yang, Yang Li, Lu Kou, Yue Liu, Qin Qin Department of Cardiovascular, Tianjin Chest Hospital, Tianjin - China Mailing Address: Qin Qin • N°. 261 Taierzhuang South Road, Jinnan District, Tianjin. 300222, Tianjin – China E-mail: qinqintj@163.com Manuscript received December 07, 2017, revised manuscript May 07, 2018, accepted May 09, 2018 DOI: 10.5935/abc.20180163 Abstract Background: Restenosis after percutaneous coronary intervention in coronary heart disease remains an unsolved problem. Clusterin (CLU) (or Apolipoprotein [Apo] J) levels have been reported to be elevated during the progression of postangioplasty restenosis and atherosclerosis. However, its role in neointimal hyperplasia is still controversial. Objective: To elucidate the role Apo J in neointimal hyperplasia in a rat carotid artery model in vivo with or without rosuvastatin administration. Methods: Male Wistar rats were randomly divided into three groups: the control group (n = 20), the model group (n = 20) and the statin intervention group (n = 32). The rats in the intervention group were given 10mg /kg dose of rosuvastatin. A 2F Fogarty catheter was introduced to induce vascular injury. Neointima formation was analyzed 1, 2, 3 and 4 weeks after balloon injury. The level of Apo J was measured by real‑time PCR, immunohistochemistry and western blotting. Results: Intimal/medial area ratio (intimal/medial, I/M) was increased after balloon-injury and reached the maximum value at 4weeks in the model group; I/M was slightly increased at 2 weeks and stopped increasing after rosuvastatin administration. The mRNA and protein levels of Apo J in carotid arteries were significantly upregulated after rosuvastatin administration as compared with the model group, and reached maximum values at 2 weeks, which was earlier than in the model group (3 weeks). Conclusion: Apo J served as an acute phase reactant after balloon injury in rat carotid arteries. Rosuvastatin may reduce the neointima formation through up-regulation of Apo J. Our results suggest that Apo J exerts a protective role in the restenosis after balloon-injury in rats. (Arq Bras Cardiol. 2018; 111(4):562-568) Keywords: Coronary Artery Dsease; Percutaneous Coronary Intervention; Rosuvastatin Calcium; Apolipoprotein J; Coronary Reestenosis; Rats. Introduction Coronary heart disease (CHD) is one of the most common cardiovascular diseases with high morbidity and mortality. Major effective techniques for myocardial revascularization are percutaneous coronary intervention (PCI) and coronary bypass surgery. Percutaneous transluminal coronary angioplasty (PTCA) is an effective treatment for CHD, but its effect in long-term is influenced by a high restenosis rate. Although drug eluting stents (DES) combined with dual antiplatelet therapy greatly reduce the occurrence of restenosis, the incidence rate still exceeds 10%. 1, 2 The mechanism underlying restenosis after PCI has been widely studied worldwide, but effective cellular or molecular targets for the treatment of restenosis after PCI urgently needs to be identified. Clusterin (CLU), or Apolipoprotein (Apo) J, is a heterodimeric glycoprotein, which is composed of α and β subunits linked by disulfide bond. 3,4 The coding gene of Apo J is located on chromosome 8p21-p12, mainly encoding two isoforms – secretory CLU (sCLU) and nuclear CLU (nCLU). 5 Apo J has been reported to be induced during the progression of postangioplasty restenosis and atherosclerosis. 6-9 However, the role of Apo J in neointimal hyperplasia is still controversial. It has been reported that Apo J could stimulate the proliferation and migration of vascular smooth muscle cell (VSMC) in CLU‑knockout mice by inhibiting the expression of p53 and p21, and promote restenosis. 10,11 On the contrary, Kim et al. 12 revealed that the overexpression of sCLU can inhibit the migration and proliferation of VSMC and inhibit the apoptosis of cells. In view of existing paradoxical findings, we aimed to elucidate the role Apo J in neointimal hyperplasia in a rat carotid artery model in vivo with or without rosuvastatin intervention. Methods Animals Male Wistar rats weighing 350-400 g were randomly divided into three groups: control group (n = 20), model group 562