JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2014, Vol. 52 ›› Issue (10): 1-8,28.doi: 10.6040/j.issn.1671-7554.0.2014.273

    Next Articles

Pro-atherosclerotic effects of streptozotocin-induced diabetes combined with chow diet on apoE-/-mice

SUN Hui, ZHAO Lei, ZHEN Xi, WANG Shasha, HUANG Shanying, HE Hong, HU Qin   

  1. Department of Cardiology, Qilu Hospital of Shandong University;
    Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Jinan 250012, Shandong, China
  • Received:2014-04-29 Revised:2014-09-14 Online:2014-10-10 Published:2014-10-10

PDF (PC)

651

Abstract: Objective To explore the effects of streptozotocin(STZ)-induced diabetes combined with chow diet on atherosclerotic lesions of apoE-/-mice. Methods After 2 weeks of chow diet, 60 male apoE-/-mice (10 weeks old) were randomly divided into two groups. Diabetic apoE-/-mice (n=30) were constructed by intraperitoneal injection of low-dose STZ for 5 consecutive days. ApoE-/-mice (n=30) injected with citrate buffer liquid served as non-diabetic controls. All mice were fed with chow diet until sacrifice (23 weeks old). Serum lipid, inflammation cytokines and blood glucose were measured. Atherosclerotic plaques in the aorta and aortic root were examined with HE staining and Oil-Red-O staining. The mRNA and protein levels of vascular smooth muscle cells (SMCs), macrophages, MMP-9/TIMP-1, TNF-α and MCP-1 in the plaques were detected with immunohistochemical staining, RT-PCR and Western blotting, respectively. Results The non-diabetic apoE-/-mice showed slight atherosclerotic lesions, while diabetic apoE-/-mice had significantly aggravated atherosclerotic lesions. Compared with non-diabetic mice, diabetic apoE-/-mice had markedly larger size of plaques, in which lipid, macrophages, type Ⅰ and Ⅲ collagens and SMCs increased,while SMCs in fiber cap decreased, and atherosclerotic plaque instability index rose. Moreover, serum IL-6 and MIF levels, TNF-α, MCP-1, MMP-2 and MMP-9 mRNA all increased while TIMP-1 decreased. Conclusion STZ-induced diabetic apoE-/-mice fed with chow diet show deteriorated atherosclerotic lesions and relatively unstable plaques.

Key words: Diabetes mellitus, Atherosclerosis, ApoE-/-mice, Streptozotocin

CLC Number: 

  • R541.4
[1] Juutilainen A, Lehto S, Ronnemaa T, et al. Similarity of the impact of type 1 and type 2 diabetes on cardiovascular mortality in middle-aged subjects[J]. Diabetes Care, 2008, 31(4): 714-719.
[2] Grundy S M, Howard B, Smith S Jr, et al. Prevention conference VI: Diabetes and cardiovascular disease executive summary conference proceeding for healthcare professionals from a special writing group of the American heart association[J]. Circulation, 2002, 105(18): 2231-2239.
[3] Toso C, Emamaullee J A, Merani S, et al. The role of macrophage migration inhibitory factor on glucose metabolism and diabetes[J]. Diabetologia, 2008, 51(11): 1937-1946.
[4] Tse J, Martin-McNaulty B, Halks-Miller M, et al. Accelerated atherosclerosis and premature calcified cartilaginous metaplasia in the aorta of diabetic male Apo E knockout mice can be prevented by chronic treatment with 17 beta-estradiol[J]. Atherosclerosis, 1999, 144(2): 303-313.
[5] Jawień J, Nastałek P, Korbut R. Mouse models of experimental atherosclerosis[J]. J Physiol Pharmacol, 2004, 55(3): 503-517.
[6] Hsueh W, Abel E D, Breslow J L, et al. Recipes for creating animal models of diabetic cardiovascular disease[J]. Circ Res, 2007, 100(10): 1415-1427.
[7] Nakashima Y, Plump A S, Raines E W, et al. ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree[J]. Arterioscler Thromb, 1994, 14(1): 133-140.
[8] Abel E D, Kaulbach H C, Tian R, et al. Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart[J]. J Clin Invest, 1999, 104(12): 1703-1714.
[9] Gallagher E J, Sun H, Kornhauser C, et al. The effect of dipeptidyl peptidase-IV inhibition on bone in a mouse model of type 2 diabetes[J]. Diabetes Metab Res Rev, 2014, 30(3): 191-200.
[10] Naveiras O, Nardi V, Wenzel P L, et al. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment[J]. Nature, 2009, 460(7252): 259-264.
[11] Kadoglou N P, Moustardas P, Kapelouzou A, et al. The anti-inflammatory effects of exercise training promote atherosclerotic plaque stabilization in apolipoprotein E knockout mice with diabetic atherosclerosis[J]. Eur J Histochem, 2013, 57(1): 3.
[12] Goldberg I J, Dansky H M. Diabetic vascular disease: an experimental objective[J]. Arterioscler Thromb Vasc Biol, 2006, 26(8): 1693-701.
[13] Tong C, Morrison A, Yan X, et al. Macrophage migration inhibitory factor deficiency augments cardiac dysfunction in Type 1 diabetic murine cardiomyocytes[J]. J Diabetes, 2010, 2(4): 267-274.
[14] Kunjathoor V V, Wilson D L, LeBoeuf R C. Increased atherosclerosis in streptozotocin-induced diabetic mice[J]. J Clin Invest, 1996, 97(7): 1767-1773.
[15] Candido R, Jandeleit-Dahm K A, Cao Z, et al. Prevention of Accelerated Atherosclerosis by Angiotensin-Converting Enzyme Inhibition in Diabetic Apolipoprotein E-Deficient Mice[J]. Circulation, 2002, 106(2): 246-253.
[16] Koïtka A, Cao Z, Koh P, et al. Angiotensin Ⅱ subtype 2 receptor blockade and deficiency attenuate the development of atherosclerosis in an apolipoprotein E-deficient mouse model of diabetes[J]. Diabetologia, 2010, 53(3): 584-592.
[17] Shen X, Bornfeldt K E. Mouse models for studies of cardiovascular complications of type 1 diabetes[J]. Ann N Y Acad Sci, 2007, 1103: 202-217.
[18] Libby P. Inflammation in atherosclerosis[J]. Nature, 2002, 420(6917): 868-874.
[19] Göran K, Hansson P L, Yan Usa Z. Innate and Adaptive Immunity in the Pathogenesis of Atherosclerosis[J]. Circulation Research, 2002, 91(4): 281-291.
[20] van der Wal A C, Becker A E, van der Loos C M, et al. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology[J]. Circulation, 1994, 89(1): 36-44.
[21] Boring L, Gosling J, Cleary M, et al. Decreased lesion formation in CCR2-/-mice reveals a role for chemokines in the initiation of atherosclerosis[J]. Nature, 1998, 394(6696): 894-897.
[22] Huber S A, Sakkinen P, Conze D, et al.Interleukin-6 exacerbates early atherosclerosis in mice[J]. Arterioscler Thromb Vasc Biol, 1999, 19(10): 2364-2367.
[23] Wong N D, Patao C, Malik S, et al. Preventable coronaryheart disease events from control of cardiovascular risk factors in US adults with diabetes (Projections from Utilizing the UKPDS Risk Engine)[J]. Am J Cardiol, 2014, 113(8): 1356-1361.
[24] Sherry C L, O'Connor J C, Kramer J M, et al. Augmented lipopolysaccharide-induced TNF-alpha production by peritoneal macrophages in type 2 diabetic mice is dependent on elevated glucose and requires p38 MAPK[J]. J Immunol, 2007, 178(2): 663-670.
[25] Gough P J, Gomez I G, Wille P T, et al. Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice[J]. J Clin Invest, 2006, 116(1): 59-69.
[26] Ding S, Zhang M, Zhao Y, et al. The role of carotid plaque vulnerability and inflammation in the pathogenesis of acute ischemic stroke[J]. Am J Med Sci, 2008, 336(1): 27-31.
[27] Matsumura S, Iwanaga S, Mochizuki S, et al. Targeted deletion or pharmacological inhibition of MMP-2 prevents cardiac rupture after myocardial infarction in mice[J]. J Clin Invest, 2005, 115(3): 599-609.
[28] Newby A C. Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates[J]. Cardiovasc Res, 2006, 69(3): 614-624.
[29] Allaire E, Forough R, Clowes M, et al. Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model[J]. J Clin Invest, 1998, 102(7): 1413-1420.
[30] Rouis M, Adamy C, Duverger N, et al. Adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E–deficient mice[J]. Circulation, 1999, 100(5): 533-540.
[31] Lemaître V, Soloway P D, D'Armiento. Increased medial degradation with pseudo-aneurysm formation in apolipoprotein E-knockout mice deficient in tissue inhibitor of metalloproteinases-1[J]. Circulation, 2003, 107(2): 333-338.
[1] DUAN Yingzhu, DONG Bo, YU Rui. Mendelian randomization study on the association of intrinsic emotions with coronary atherosclerosis risk in patients with rheumatoid arthritis [J]. Journal of Shandong University (Health Sciences), 2026, 64(4): 63-71.
[2] LI Xiping, QIU Mei, HUANG Ruifeng, LIN Huihui, LIU Sisi, LUO Hongying, WANG Yuyue, WANG Min, YANG Xiaotong. Research progress on the mechanism of berberines anti-atherosclerosis effects based on the synergistic effect of lipid deposition inhibition and metabolic clearance [J]. Journal of Shandong University (Health Sciences), 2025, 63(9): 77-83.
[3] MENG Xiaomei, HAO Yaping, WANG Liang, YU Xiao, TANG Yuxiao. Correlation between the levels of serum Isthmin1, Gremlin2 and retinopathy in type 2 diabetic patients [J]. Journal of Shandong University (Health Sciences), 2025, 63(9): 102-107.
[4] WANG Mengxing, XUE Fuzhong, YANG Fan. Blood glucose concentration prediction method for type 1 diabetes mellitus based on multi-modal cross-attention mechanism fusion [J]. Journal of Shandong University (Health Sciences), 2025, 63(8): 41-50.
[5] SHEN Lujia, LU Tianwei, GONG Weiming, ZHAO Yansong, WANG Shukang, YUAN Zhongshang. Application of metabolomic risk score in predicting cardiovascular outcomes in patients with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2025, 63(8): 69-78.
[6] CHEN Yingying, WANG Lu, HU Xifeng, ZHU Gaopei, XUE Fuzhong. A Bayesian network-based risk prediction study of stroke in patients with type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2025, 63(8): 94-102.
[7] CHEN Xujun, HE Guowei. Focus on further more use of arterial grafts in coronary artery bypass grafting in patients with coronary heart disease in China [J]. Journal of Shandong University (Health Sciences), 2025, 63(5): 1-5.
[8] LU Shengxun, XING Yachuang, LUO Junhui, LIU Jie, HE Houle, WANG Zhiqiang, ZHANG Na. Diabetic patients arterial grafts in coronary artery bypass grafting: current research status [J]. Journal of Shandong University (Health Sciences), 2025, 63(5): 33-39.
[9] DU Aijia, ZHANG Man, CHEN He, WANG Lixin, SHANG Yingshu. miR-1270-targeted regulation of angiopoietin-like protein 7 inhibits macrophage inflammation and lipid accumulation [J]. Journal of Shandong University (Health Sciences), 2025, 63(2): 1-9.
[10] LIN Xiaoqian, FENG Maoyan, MOU Zheng. Pharmaceutical characteristics and clinical utility of dipeptidyl peptidase-4 inhibitors [J]. Journal of Shandong University (Health Sciences), 2024, 62(12): 43-48.
[11] LI Jinquan, GAO Meifang, YAN Fei, DONG Ming. Frequency and risk factors of muscle cramp in 136 cases of type 2 diabetes mellitus [J]. Journal of Shandong University (Health Sciences), 2023, 61(5): 20-24.
[12] XU Tianqi, CHANG Na, ZHANG Shuai, LI Sha, JIAO Bingxuan, YU Xinxin, WANG Ximing. Identification of carotid high-risk plaques by non-alcoholic fatty liver disease based on CTA [J]. Journal of Shandong University (Health Sciences), 2023, 61(12): 36-43.
[13] HAN Mei, MENG Weijing, TAO Zikun, YANG Xi, XU Yaqi, MU Huaxia, BU Weixiao, WANG Suzhen, SHI Fuyan. Causal mediation analysis with multiple-mediator of hypertension and depression between type 2 diabetes mellitus and cognitive function based on G-computation [J]. Journal of Shandong University (Health Sciences), 2023, 61(10): 101-108.
[14] WU Hong, ZHANG Zhengduo, TANG Yanjin, QI Shaojun, GAO Xibao. Potential intervention effects of 5-methyltetrahydrofolate on atherosclerosis in rats [J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 6-13.
[15] LI Tao, YANG Chunlin, DU Tong, LI Heng, WANG Congcong, LI Xiaoli, DUAN Ruisheng,ZHANG Peng. Effects of diabetes mellitus on the subsets and function of NK cells in myasthenia gravis [J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 31-36.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd