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Cigarette Smoke Exposure, but Not High Fat Diet, is Able to Induce Atherosclerosis in Wild-Type Rats

1Faculty of Medicine, Universitas Diponegoro, Indonesia

2Departement of Clinical Pathology, Faculty of Medicine, Universitas Diponegoro, Indonesia

3Departement of Oncology Surgery, Faculty of Medicine, Universitas Diponegoro, Indonesia

4 Departement of Pharmacology, Faculty of Medicine, Universitas Diponegoro, Indonesia

5 Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Diponegoro, Indonesia

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Received: 1 Sep 2022; Revised: 17 Oct 2022; Accepted: 18 Oct 2022; Available online: 30 Dec 2022; Published: 30 Dec 2022.
Open Access Copyright (c) 2022 Journal of Biomedicine and Translational Research
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Background: High-fat diet (HFD) and cigarette smoke exposure (CSE) have been used to induce atherosclerosis in wild-type (WT) rats however, their effectivity remains unclear.

Objective: To confirm and compare the effectivity of HFD and CSE on both the histopathology of aorta and the level of malondialdehyde (MDA) in WT rats.

Methods: Thirty-six WT Wistar rats were divided into four main groups (K0, K1, K2, and K3) and four subgroups (K3A, K3B, K3C, and K3D). The negative control group (K0) was fed with regular diet. Group K1 was treated with an intravenous adrenaline followed by high-fat diet (HFD), K2 was fed with regular diet and given CSE, while K3 was treated with a combination of CSE and HFD. The serum and cardiac MDA levels were measured using ELISA. Hematoxylin eosin and oil red O staining of aorta were done for measuring of the intima-media thickness (IMT) ratio and for counting of foam cells, respectively. 

Results: Both serum and cardiac tissue MDA levels in either K1, K2, or K3 were significant higher (p<0.01) than that of in K0. IMT ratio in K3 was significant higher compared to other groups (p<0.01). Foam cell numbers were significant higher in K2 and K3 groups than that of in either K0 or K1 (p<0.01).

Conclusion: While the HFD fails to induce atherosclerosis in WT rats for 28 days, either CSE or combination of CSE and HFD is able to induce it, and the combination is better than alone.


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Keywords: Atherosclerosis; intima-media thickness ratio; foam cells; malondialdehyde; cigarette smoke exposure; high fat diet

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  1. Herrington W, Lacey B, Sherliker P, et al. Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease. Circ Res. 2016 Feb 19;118(4):535–46.
  2. Kalanuria AA, Nyquist P, Ling G. The prevention and regression of atherosclerotic plaques: Emerging treatments. Vol. 8, Vascular Health and Risk Management. 2012. p. 549–61.
  3. Zhao Y, Qu H, Wang Y, Xiao W, Zhang Y, Shi D. Small rodent models of atherosclerosis. Vol. 129, Biomedicine and Pharmacotherapy. Elsevier Masson SAS; 2020.
  4. Gisterå A, Ketelhuth DFJ, Malin SG, Hansson GK. Animal Models of Atherosclerosis–Supportive Notes and Tricks of the Trade. Circ Res. 2022 Jun 10;130(12):1869–87.
  5. Getz GS, Reardon CA. Animal models of Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology. 2012 May;32(5):1104-15.
  6. Gwala F, Sibuor W, Olabu B, Pulei A, Ogeng’o J. Hibiscus ameliorates salt-induced carotid intima-media thickness in albino rats. Anatomy. 2019 Aug 1;13(2):92–7.
  7. Nagendra Nayak IM, Rajasekhar C, Jetti R. Anti-atherosclerotic potential of aqueous extract of Cinnamomum zeylanicum bark against glucocorticoid induced atherosclerosis in wistar rats. Journal of Clinical and Diagnostic Research. 2017 May 1;11(5):FC19–23.
  8. Liu Z, Chen T, Niu H, Ren W, Li X, Cui L, et al. The establishment and characteristics of rat model of atherosclerosis induced by hyperuricemia. Stem Cells Int. 2016;2016.
  9. J LM, Chen H, Li D, et al. Novel Rat Models for Atherosclerosis. Vol. 2. 2018.
  10. Anazawa T, Dimayuga PC, Li H, Tani S, Bradfield J, Chyu KY, et al. Effect of exposure to cigarette smoke on carotid artery intimal thickening: The role of inducible NO synthase. Arterioscler Thromb Vasc Biol. 2004 Sep;24(9):1652–8.
  11. Lynch J, Jin L, Richardson A, et al. Tobacco Smoke and Endothelial Dysfunction: Role of Aldehydes? Vol. 22, Current Hypertension Reports. Springer; 2020.
  12. Winarsi H, Yuniaty A, Nuraeni I. Improvement of Antioxidant and Immune Status of Atherosclerotic Rats Adrenaline and Egg-Yolks -Induced Using Cardamom-Rhizome-Ethanolic-Extract: An Initial Study of Functional Food. Agriculture and Agricultural Science Procedia. 2016;9:264–70.
  13. Yao BC, Meng LB, Hao ML, et al. Chronic stress: a critical risk factor for atherosclerosis. Vol. 47, Journal of International Medical Research. SAGE Publications Ltd; 2019. p. 1429–40.
  14. Gallo G, Volpe M, Savoia C. Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications. Vol. 8, Frontiers in Medicine. Frontiers Media S.A.; 2022.
  15. Othman ZA, Ghazali WSW, Noordin L, et al. Phenolic compounds and the anti-atherogenic effect of bee bread in high-fat diet-induced obese rats. Antioxidants. 2020 Jan 1;9(1).
  16. Wu SS, Kor CT, Chen TY, et al. Relationships between Serum Uric Acid, Malondialdehyde Levels, and Carotid Intima-Media Thickness in the Patients with Metabolic Syndrome. Oxid Med Cell Longev. 2019;2019.
  17. OECD/OCDE 412 OECD GUIDELINES ON THE TESTING OF CHEMICALS 28-day (subacute) inhalation toxicity study [Internet]. 2018. Available from:
  18. Nithya A, Kayalvizhi R. Measurement of lower and upper IMT from Ultrasound Video Frames. Biomedical and Pharmacology Journal. 2015 Jun 1;8(1):355–64.
  19. Shen S, Li H, Ge S, Huang H, Zhang H, Li F, et al. 18 F fluorodeoxyglucose positron emission tomography for the detection of inflammatory lesions of the arterial vessel walls in Wistar rats . Exp Ther Med. 2021 Feb 19;21(4).
  20. von Holt K, Lebrun S, Stinn W, Conroy L, Wallerath T, Schleef R. Progression of atherosclerosis in the Apo E-/- model: 12-Month exposure to cigarette mainstream smoke combined with high-cholesterol/fat diet. Atherosclerosis. 2009 Jul;205(1):135–43.
  21. Zhou MS, Chadipiralla K, Mendez AJ, Jaimes EA, Silverstein RL, Webster K, et al. Nicotine potentiates proatherogenic effects of oxLDL by stimulating and upregulating macrophage CD36 signaling. Am J Physiol Heart Circ Physiol [Internet]. 2013;305:563–74.
  22. Ardiana M, Pikir BS, Santoso A, et al. The effect of subchronic cigarette smoke exposure on oxidative stress parameters and endothelial nitric oxide synthase in a rat aorta. ARYA Atheroscler. 2021 Jan 1;17(1). 10.22122/arya.v17i0.2150
  23. Lee J, Cooke JP. The role of nicotine in the pathogenesis of atherosclerosis. Vol. 215, Atherosclerosis. 2011. p. 281–3.
  24. Zhao L, Dai W, Carreno J, Shi J, Kleinman MT, Kloner RA. Acute administration of nicotine induces transient elevation of blood pressure and increases myocardial infarct size in rats. Heliyon. 2020 Nov 1;6(11).
  25. Cunningham KS, Gotlieb AI. The role of shear stress in the pathogenesis of atherosclerosis. Vol. 85, Laboratory Investigation. 2005. p. 9–23.
  26. Heeschen C, Weis M, Cooke JP. Nicotine promotes arteriogenesis. J Am Coll Cardiol. 2003 Feb 5;41(3):489–96.
  27. Iwano S, Nukaya M, Saito T, Asanuma F, Kamataki T. A possible mechanism for atherosclerosis induced by polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun. 2005 Sep 16;335(1):220–6.
  28. Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Vol. 24, Current Biology. Cell Press; 2014.
  29. Fetterman JL, Sammy MJ, Ballinger SW. Mitochondrial toxicity of tobacco smoke and air pollution. Toxicology. 2017 Nov 1;391:18–33.
  30. Carboxyhemoglobin Toxicity - PubMed [Internet]. [cited 2022 Sep 2]. Available from:
  31. Lau PP, Li L, Merched AJ, Zhang AL, Ko KWS, Chan L. Nicotine induces proinflammatory responses in macrophages and the aorta leading to acceleration of atherosclerosis in low-density lipoprotein receptor-/- mice. Arterioscler Thromb Vasc Biol. 2006 Jan;26(1):143–9.
  32. Mahmoudi M, Ebrahimzadeh MA, Pourmorad F, Rezaie N, Mahmoudi MA, Ebrahimzadeh MA. Anti-inflammatory and analgesic effects of egg yolk: a comparison between organic and machine made. Eur Rev Med Pharmacol Sci. 2013 Feb;17(4):472-6. PMID: 23467945
  33. Miras AD, Seyfried F, Phinikaridou A, Andia ME, Christakis I, Spector AC, et al. Rats fed diets with different energy contribution from fat do not differ in adiposity. Obes Facts. 2014 Nov 13;7(5):302–10.

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