| Recent studies showed that atherosclerosis was associated with inflammation. The disruption of plaques and the widespread of inflammation were the most important reason leading to acute coronary syndrome (ACS). Inflammation especially T cells-derived inflammation plays an important role in the pathogenesis of plaque rupture. Previous studies showed that most of the T cells in atherosclerotic plaques are CD4+ helper T lymphocytes. Studies in our lab indicated that after activation CD4+T cell in the peripheral blood of patients with acute coronary syndrome displayed higher current density of Kv1.3 channel compared with it in healthy controls. Kv1.3 channel blocker could suppress the function of activated CD4+T cell in the peripheral blood of patients with acute coronary syndrome in vitro. In addition, the Kv1.3 protein expression of T cells in the peripheral blood of patients with acute coronary syndrome was also increased significantly compared to those in the healthy controls. However, whether blocking Kvl.3 channel could have effects on the progress of atherosclerosis has not been investigated. In this study, rat atherosclerosis model was established. We investigated the effects of PAP-1, a small molecule voltage-gated potassium channel Kv1.3 Blocker, on the progress of atherosclerosis in a rat model and its potential mechanism. Objective To establish a rat atherosclerosis model with unstable plagues.Methods Forty male Wistar rats were randomly divided into four groups:control group (Group C), atherosclerosis model group (Group A1, A2, A3), n=10 each. Rats in Group A1 were fed with high fat diet NO.1 while rats in Group A2 and Group A3 were fed with high fat diet NO.2. All the rats in atherosclerosis model group were treated with Vitamin D3 together with high fat diet. The aorta intimal of rats in Group A3 was injuried after 7 days of high fat diet feeding. Rats in Group C were fed with a standard diet. After 16 weeks, the plasma lipids, growth and body weight of rats were measured and the morphological changes of rat thoracic aorta were observed. The frequency of T lymphocytes in rat peripheral blood was detected.Results Rat plasma levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in Group A1, Group A2 and Group A3 were higher than those in Group C. Because of the decreased appetite,6 rats in Group A1 died and the left 4 rats grew slowly. Rats in Group A2 and Group A3 were in obesity, but rats in Group C were normal. Unstable atherosclerotic plaques were formed in the rat thoracic aorta in Group A3. In contrast, only aorta sclerosis was observed in the rat thoracic aorta in Group A1 and Group A2. Moreover, rats in Group C displayed normal thoracic aorta. Compared to the Group A3, the frequencies of T cells in rat peripheral blood of Group C, Group Al and Group A2 were decreased significantly. There was no significant difference in the frequencies of T cells in rat peripheral blood among Group C, Group A1 and Group A2.Conclusions The components of high fat diet and the vascular injury played an important role in the establishment of a rat atherosclerosis model with unstable plagues. A rat atherosclerosis model with unstable plagues could be established with a special high fat diet feeding plus VitD3 and vascular injury.[keyword] Unstable atherosclerotic plaques; Rat model; High fat diet; BalloonObjective To investigate the effect of PAP-1, a small molecule voltage-gated potassium channel Kvl.3 Blocker, on the progress of atherosclerosis in a rat model.Methods Thirty male Wistar rats were randomly divided into three groups: control group(Group C), atherosclerosis model group(Group A), atherosclerosis model+PAP-1 treated group(Group P). Rat atherosclerosis model was established. After 16 weeks, the rat plasma lipids were measured and the pathological changes of rat aortic arch and left common carotid artery were studied. The immunophenotype changes of lymphocytes in rat peripheral blood were analyzed. Serum levels of high sensitive C-reactive protein (hs-CRP), IFN-y and perforin were assayed by competitive enzyme-linked immunosorbent assay and western blot technique was used to detect the express of Kvl.3 protein in rat lymphocytes.Results The rat plasma levels of C-reactive protein (CRP), total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in Group A and Group P were increased significantly compared with that in Group C. Unstable atherosclerotic plaques were observed in rat left common carotid artery and aortic arch in Group A. In contrast, only aorta sclerosis was observed in rat left common carotid artery and aortic arch in Group P. Moreover, rats in Group C displayed normal aortic arch and left common carotid artery. The frequencies of CD3+CD4+CD28-T cells in rat peripheral blood in Group C were significantly decreased compared to that in the Group A and Group P, which was no significant difference in between Group A and Group P. The higher levels of perform were found in the rat peripheral circulation in the Group A and Group P compared to that in the Group C. Moreover, PAP-1 decreased the level of perform in the Group P compared to that in the Group A. In contrast, there was no significant difference among the levels of IFN-r in these three groups. The Kvl.3 protein expression of rat lymphocytes in the peripheral circulation were increased in Group P and Group A. The Kv1.3 protein expression in rat lymphocytes was decreased in Group P compared to Group A.Conclusions voltage-gated potassium channel Kv1.3 blocker PAP-1 can suppress the progress of atherosclerosis in rat model. It may be due to its suppression of the expression of Kv1.3 protein in rat T lymphocytes and thus suppress the activation and some functions of rat T lymphocytes.
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