Occlusal disharmony accelerates the initiation of atherosclerosis in apoE knockout rats

Lipids in Health and Disease

Manabu Morita³  Takaaki Tomofuji²  Tetsuji Azuma³  Shinsuke Mizutani³  Koichiro Irie¹  Kenta Kasuyama³  Yasumasa Endo³  Toshiki Yoneda³  Daisuke Ekuni³ 

[1]Department of Preventive Dentistry and Dental Public Health, Aichi-Gakuin University, Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan

[2]Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

[3]Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

关键词: Vascular cell Adhesion molecule-1;    Toll-like receptor;    Stress;    Occlusion;    Atherosclerosis;    Apolipoprotein E;   

Others  :  1152246
DOI  :  10.1186/1476-511X-13-144

 received in 2014-05-21, accepted in 2014-09-02,  发布年份 2014

【 摘 要 】

Background

Psychosocial stress is one of the risk factors for atherosclerosis. As occlusal disharmony induces psychological stress, we hypothesized that psychological stress by occlusal disharmony accelerates atherosclerosis. The aim of this study was to investigate the effects of occlusal disharmony on the initiation of atherosclerosis in apolipoprotein E (apoE) knockout rats.

Methods

Fourteen male apoE-knockout rats (age; 8 weeks) (Sprague–Dawley strain background) were divided into two groups of seven rats: the occlusal disharmony group and the no treatment (control) group. In the occlusal disharmony group, the maxillary molar cusps were cut off for the 8-week experimental period.

Results

In the occlusal disharmony group, the percentages of the area of total aortic lumen occupied by plaques and lipid were significantly higher than those in the control group (p < 0.05, t-test). The occlusal disharmony group also showed significantly higher serum levels of very low-density lipoprotein-cholesterol (VLDL) and low-density lipoprotein-cholesterol (LDL), plasma levels of corticosterone (1.9, 1.3 and 1.3 times, respectively), higher aortic protein expression levels of vascular cell adhesion molecule-1 (VCAM1) and intercellular adhesion molecule-1 (ICAM1) (1.5 and 1.4 times, respectively), and higher aortic gene expression of levels of VCAM1 and Toll-like receptor 4 (TLR4) (1.9 and 4.3 times, respectively), as compared to the control group (p < 0.05). However, there were no significant differences in serum levels of oxidized LDL, reactive oxygen metabolites and C-reactive protein between the two groups.

Conclusion

In apoE knockout rats, occlusal disharmony may induce VCAM1, ICAM1 and TLR4 expression and accelerate the initiation of atherosclerosis.

【 授权许可】

   
2014 Ekuni et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Libby P, Ridker PM, Hansson GK: Progress and challenges in translating the biology of atherosclerosis. Nature 2011, 473(7347):317-325.
• [2]Sun X, Belkin N, Feinberg MW: Endothelial microRNAs and atherosclerosis. Curr Atheroscler Rep 2013, 15(12):372.
• [3]Tabas I, Williams KJ, Boren J: Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 2007, 116(16):1832-1844.
• [4]Higashimori M, Tatro JB, Moore KJ, Mendelsohn ME, Galper JB, Beasley D: Role of toll-like receptor 4 in intimal foam cell accumulation in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2011, 31(1):50-57.
• [5]Steinberg D, Witztum JL: Oxidized low-density lipoprotein and atherosclerosis. Arterioscler Thromb Vasc Biol 2010, 30(12):2311-2316.
• [6]Bernhard D, Wang XL: Smoking, oxidative stress and cardiovascular diseases—do anti-oxidative therapies fail? Curr Med Chem 2007, 14(16):1703-1712.
• [7]Nicolls MR, Haskins K, Flores SC: Oxidant stress, immune dysregulation, and vascular function in type I diabetes. Antioxid Redox Signal 2007, 9(7):879-889.
• [8]Mügge A, Brandes RP, Böger RH, Dwenger A, Bode-Böger S, Kienke S, Frölich JC, Lichtlen PR: Vascular release of superoxide radicals is enhanced in hypercholesterolemic rabbits. J Cardiovasc Pharmacol 1994, 24(6):994-998.
• [9]Buday A, Orsy P, Godó M, Mózes M, Kökény G, Lacza Z, Koller A, Ungvári Z, Gross ML, Benyó Z, Hamar P: Elevated systemic TGF-beta impairs aortic vasomotor function through activation of NADPH oxidase-driven superoxide production and leads to hypertension, myocardial remodeling, and increased plaque formation in apoE(−/−) mice. Am J Physiol Heart Circ Physiol 2010, 299(2):H386-H395.
• [10]Huang A, Sun D, Kaley G, Koller A: Superoxide released to high intra-arteriolar pressure reduces nitric oxide-mediated shear stress- and agonist-induced dilations. Circ Res 1998, 83(9):960-965.
• [11]Ekuni D, Tomofuji T, Sanbe T, Irie K, Azuma T, Maruyama T, Tamaki N, Murakami J, Kokeguchi S, Yamamoto T: Vitamin C intake attenuates the degree of experimental atherosclerosis induced by periodontitis in the rat by decreasing oxidative stress. Arch Oral Biol 2009, 54(5):495-502.
• [12]Ekuni D, Tomofuji T, Sanbe T, Irie K, Azuma T, Maruyama T, Tamaki N, Murakami J, Kokeguchi S, Yamamoto T: Periodontitis-induced lipid peroxidation in rat descending aorta is involved in the initiation of atherosclerosis. J Periodontal Res 2009, 44(4):434-442.
• [13]Corrado E, Rizzo M, Coppola G, Fattouch K, Novo G, Marturana I, Ferrara F, Novo S: An update on the role of markers of inflammation in atherosclerosis. J Atheroscler Thromb 2010, 17(1):1-11.
• [14]Libby P: Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 2012, 32(9):2045-2051.
• [15]Hansson GK, Hermansson A: The immune system in atherosclerosis. Nat Immunol 2011, 12(3):204-212.
• [16]Meng Z, Yan C, Deng Q, Dong X, Duan ZM, Gao DF, Niu XL: Oxidized low-density lipoprotein induces inflammatory responses in cultured human mast cells via Toll-like receptor 4. Cell Physiol Biochem 2013, 31(6):842-853.
• [17]Rozanski A, Blumenthal JA, Davidson KW, Saab PG, Kubzansky L: The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. J Am Coll Cardiol 2005, 45(5):637-651.
• [18]Rosengren A, Hawken S, Ounpuu S, Sliwa K, Zubaid M, Almahmeed WA, Blackett KN, Sitthi-amorn C, Sato H, Yusuf S, INTERHEART investigators: Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case–control study. Lancet 2004, 364(9438):953-962.
• [19]Kumari M, Grahame-Clarke C, Shanks N, Marmot M, Lightman S, Vallance P: Chronic stress accelerates atherosclerosis in the apolipoprotein E deficient mouse. Stress 2003, 6(4):297-299.
• [20]Zhang T, Chen Y, Liu H, Zhou Z, Zhai Y, Yang J: Chronic unpredictable stress accelerates atherosclerosis through promoting inflammation in apolipoprotein E knockout mice. Thromb Res 2010, 126(5):386-392.
• [21]Ekuni D, Furuta M, Irie K, Azuma T, Tomofuji T, Murakami T, Yamashiro T, Ogura T, Morita M: Relationship between impacts attributed to malocclusion and psychological stress in young Japanese adults. Eur J Orthod 2011, 33(5):558-563.
• [22]Yoshihara T, Matsumoto Y, Ogura T: Occlusal disharmony affects plasma corticosterone and hypothalamic noradrenaline release in rats. J Dent Res 2001, 80(12):2089-2092.
• [23]Onozuka M, Watanabe K, Fujita M, Tonosaki K, Saito S: Evidence for involvement of glucocorticoid response in the hippocampal changes in aged molarless SAMP8 mice. Behav Brain Res 2002, 131(1–2):125-129.
• [24]Ekuni D, Endo Y, Tomofuji T, Azuma T, Irie K, Kasuyama K, Morita M: Effects of apoE Deficiency and Occlusal Disharmony on Amyloid-Beta Production and Spatial Memory in Rats. PLoS ONE 2013, 8(9):e74966.
• [25]Ekuni D, Endo Y, Irie K, Azuma T, Tamaki N, Tomofuji T, Morita M: Imbalance of oxidative/anti-oxidative status induced by periodontitis is involved in apoptosis of rat submandibular glands. Arch Oral Biol 2010, 55(2):170-176.
• [26]Ekuni D, Tomofuji T, Irie K, Azuma T, Endo Y, Kasuyama K, Morita M: Occlusal disharmony increases amyloid-β in the rat hippocampus. Neuromolecular Med 2011, 13(3):197-203.
• [27]Irie K, Ekuni D, Tomofuji T, Azuma T, Endo Y, Kasuyama K, Morita M: Occlusal disharmony induces BDNF level in rat submandibular gland. Arch Oral Biol 2011, 56(1):35-40.
• [28]Usui S, Hara Y, Hosaki S, Okazaki M: A new on-line dual enzymatic method for simultaneous quantification of cholesterol and triglycerides in lipoproteins by HPLC. J Lipid Res 2002, 43(5):805-814.
• [29]Tomofuji T, Ekuni D, Azuma T, Irie K, Endo Y, Kasuyama K, Yoneda T, Morita M: Involvement of toll-like receptor 2 and 4 in association between dyslipidemia and osteoclast differentiation in apolipoprotein E deficient rat periodontium. Lipids Health Dis 2013, 12:1. BioMed Central Full Text
• [30]Ekuni D, Tomofuji T, Endo Y, Kasuyama K, Irie K, Azuma T, Tamaki N, Mizutani S, Kojima A, Morita M: Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model. Arch Oral Biol 2012, 57(12):1615-1622.
• [31]Endo Y, Tomofuji T, Ekuni D, Irie K, Azuma T, Tamaki N, Yamamoto T, Morita M: Experimental periodontitis induces gene expression of proinflammatory cytokines in liver and white adipose tissues in obesity. J Periodontol 2010, 81(4):520-526.
• [32]Ekuni D, Tomofuji T, Irie K, Kasuyama K, Umakoshi M, Azuma T, Tamaki N, Sanbe T, Endo Y, Yamamoto T, Nishida T, Morita M: Effects of periodontitis on aortic insulin resistance in an obese rat model. Lab Invest 2010, 90(3):348-359.
• [33]Xu XH, Shah PK, Faure E, Equils O, Thomas L, Fishbein MC, Luthringer D, Xu XP, Rajavashisth TB, Yano J, Kaul S, Arditi M: Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL. Circulation 2001, 104(25):3103-3108.
• [34]Edfeldt K, Swedenborg J, Hansson GK, Yan ZQ: Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation 2002, 105(10):1158-1161.
• [35]Catar RA, Müller G, Heidler J, Schmitz G, Bornstein SR, Morawietz H: Low-density lipoproteins induce the renin-angiotensin system and their receptors in human endothelial cells. Horm Metab Res 2007, 39(11):801-805.
• [36]Estruch M, Sánchez-Quesada JL, Ordóñez-Llanos J, Benítez S: Ceramide-enriched LDL induces cytokine release through TLR4 and CD14 in monocytes. Similarities with electronegative LDL. Clin Investig Arterioscler 2014, 26(3):131-137.
• [37]Springer TA: Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 1994, 76(2):301-314.
• [38]Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M, Davis V, Gutierrez-Ramos JC, Connelly PW, Milstone DS: A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest 2001, 107(10):1255-1262.
• [39]Allen S, Khan S, Al-Mohanna F, Batten P, Yacoub M: Native low density lipoprotein-induced calcium transients trigger VCAM-1 and E-selectin expression in cultured human vascular enothelial cells. J Clin Invest 1998, 101(5):1064-1075.
• [40]Okutsu M, Lira VA, Higashida K, Peake J, Higuchi M, Suzuki K: Corticosterone accelerates atherosclerosis in the apolipoprotein E-deficient mouse. Atherosclerosis 2014, 232(2):414-419.
• [41]Oda H, Suzuki Y, Shibata T, Yoshida A: Glucocorticoid-dependent induction of HMG-CoA reductase and malic enzyme gene expression by polychlorinated biphenyls in rat hepatocytes. J Nutr Biochem 1999, 10(11):644-653.
• [42]Siperstein MD, Fagan VM: Feedback control of mevalonate synthesis by dietary cholesterol. J Biol Chem 1966, 241(3):602-609.
• [43]Morikawa S, Umetani M, Nakagawa S, Yamazaki H, Suganami H, Inoue K, Kitahara M, Hamakubo T, Kodama T, Saito Y: Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells. J Atheroscler Thromb 2000, 7(3):138-144.
• [44]Chen K, Keaney JF Jr: Evolving concepts of oxidative stress and reactive oxygen species in cardiovascular disease. Curr Atheroscler Rep 2012, 14(5):476-483.
• [45]Mitra S, Goyal T, Mehta JL: Oxidized LDL, LOX-1 and atherosclerosis. Cardiovasc Drugs Ther 2011, 25(5):419-429.
• [46]Ross R: Atherosclerosis—an inflammatory disease. N Engl J Med 1999, 340(2):115-126.
• [47]Andersson IJ, Sankaralingam S, Davidge ST: Restraint stress up-regulates lectin-like oxidized low-density lipoprotein receptor-1 in aorta of apolipoprotein E-deficient mice. Stress 2010, 13(5):454-460.
• [48]Grad E, Danenberg HD: C-reactive protein and atherothrombosis: Cause or effect? Blood Rev 2013, 27(1):23-29.
• [49]Holmlund A, Lind L: Number of teeth is related to atherosclerotic plaque in the carotid arteries in an elderly population. J Periodontol 2012, 83(3):287-291.
• [50]Chin UJ, Ji S, Lee SY, Ryu JJ, Lee JB, Shin C, Shin SW: Relationship between tooth loss and carotid intima-media thickness in Korean adults. J Adv Prosthodont 2010, 2(4):122-127.