Cilostazol inhibits accumulation of triglycerides in a rat model of carotid artery ligation Hiroki Tanaka, MD, PhD, Nobuhiro Zaima, PhD, Hideki Ito, PhD,

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Presentation transcript:

Cilostazol inhibits accumulation of triglycerides in a rat model of carotid artery ligation Hiroki Tanaka, MD, PhD, Nobuhiro Zaima, PhD, Hideki Ito, PhD, Katsuji Hattori, PhD, Naoto Yamamoto, MD, Hiroyuki Konno, MD, PhD, FACS, Mitsutoshi Setou, MD, PhD, Naoki Unno, MD, PhD, FACS Journal of Vascular Surgery Volume 58, Issue 5, Pages 1366-1374 (November 2013) DOI: 10.1016/j.jvs.2013.01.033 Copyright © 2013 Society for Vascular Surgery Terms and Conditions

Fig 1 Schema of carotid artery ligation. The carotid artery on one side was isolated from the perivascular tissue and ligated near the carotid bifurcation to stop the blood flow. A 5-mm-long section of arterial tissue proximal to the ligation was harvested (double arrow). Journal of Vascular Surgery 2013 58, 1366-1374DOI: (10.1016/j.jvs.2013.01.033) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

Fig 2 Triglyceride (TG) content is decreased in the carotid artery by cilostazol (CLZ). The amount of TGs in the arterial tissue was quantified using the colorimetric method. The carotid artery was harvested 4 weeks after the operation from the rats in the CLZ-treated group and the control group (n = 6 for each group). Data are reported as means ± standard deviation. Significant intergroup differences in the ion intensity ratio were determined by the Tukey-Kramer test; *P < .05, indicating a significant difference. Journal of Vascular Surgery 2013 58, 1366-1374DOI: (10.1016/j.jvs.2013.01.033) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

Fig 3 Imaging mass spectrometry reveals accumulation of triglycerides (TGs) in the ligated carotid artery tissue. Combined mass spectra were obtained from the carotid arterial tissue sections with and without ligation and with (+) and without (−) cilostazol (CLZ) treatment. a, Representative mass spectrum patterns of the tissues. Five peaks in the mass spectrum patterns (m/z 616, 782, 798, 879, and 881) of the carotid artery tissues were selected for investigating the distribution of the molecules. b, Imaging mass spectrometry and optical images of a frozen section (8 μm). Distributions of phosphatidylcholine (PC) (diacyl 16:0/18:1), heme B, TG(52:3)+K, and TG(52:2)+K in the analyzed tissue of the control group (CLZ[−]) and the cilostazol group (CLZ[+]) are shown 4 weeks after the operation. Scale bar = 5 mm. Journal of Vascular Surgery 2013 58, 1366-1374DOI: (10.1016/j.jvs.2013.01.033) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

Fig 4 Contents of heme B (a), triglyceride (TG)(52:3) (b), and TG(52:2) (c). Imaging mass spectrometry reveals amelioration of heme B decrease and inhibition of TG accumulation in the carotid artery by cilostazol (CLZ). The ion intensity of each molecule is standardized to that of phosphatidylcholine (PC) (diacyl 16:0/18:1) obtained from the same sample and expressed as a ratio of relative intensity (RRI) in both groups (n = 6 for each group). Data are reported as means ± standard deviation. Significance was determined by a two-tailed t-test. *P < .05 indicates a significant difference. Journal of Vascular Surgery 2013 58, 1366-1374DOI: (10.1016/j.jvs.2013.01.033) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

Fig 5 Cilostazol (CLZ) inhibits neointimal formation in carotid arteries. a, Representative light photomicrographs of carotid arteries from the control group (CLZ[−]) and CLZ group (CLZ[+]) obtained using elastica van Gieson method. Bar = 50 μm. b, Morphometry of the carotid arteries of rats in the control group (CLZ[−]) and CLZ group (CLZ[+]) 4 weeks after the operation. Intergroup comparison is shown of (b) the total area of the intima plus media and (c) the thickness ratio of intima/media (n = 6 for each group). Data are reported as means ± standard deviation. Significance of the intergroup differences in the area was determined by two-tailed t-test; *P < .05 indicates a significant difference. Journal of Vascular Surgery 2013 58, 1366-1374DOI: (10.1016/j.jvs.2013.01.033) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

Fig 6 Cilostazol (CLZ) inhibits neointimal formation of adventitial vasa vasorum (VV) in carotid arteries. Representative light photomicrographs of carotid arteries of rats in the control group (CLZ[−]) and CLZ group (CLZ[+]). Adventitial VV are observed in high-power fields by using the elastica van Gieson method. Bar = 100 μm. N, Nerve. Journal of Vascular Surgery 2013 58, 1366-1374DOI: (10.1016/j.jvs.2013.01.033) Copyright © 2013 Society for Vascular Surgery Terms and Conditions