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Licensed Unlicensed Requires Authentication Published by De Gruyter June 25, 2021

Analysis of HMGB-1 level before and after providing atorvastatin standard therapy in coronary artery disease patients with type-2 diabetes mellitus compared to without type-2 diabetes mellitus

  • Widya Handayani , Suharjono EMAIL logo and Mohammad Yogiarto



Coronary artery disease (CAD) is one of the main causes of death from cardiovascular disease, because heart attacks result in atherosclerosis which causes narrowing of the arteries. Atorvastatin has a pleiotropic effect as anti-inflammatory through one of the target levels of High Mobility Group Box-1 (HMGB-1). This prospective observational study aimed to analyze the effect of atorvastatin on serum HMGB-1 levels in CAD.


Samples were collected from prospective observation pre–post study in May–July 2018 with consecutive sampling method. Serum HMGB-1 levels were measured in patients with CAD who were given atorvastatin for CAD with type-2 diabetes mellitus compared without type-2 diabetes mellitus in a patient ward. Blood was collected on admission day and before the patient left the hospital. After centrifugation, serum samples were stored at −80 °C before measurement. We used an ELISA kit (IBL International) to determine HMGB-1 concentrations. This research protocol has been approved by the Ethical Committee of Dr. Soetomo General Hospital, Surabaya.


We enrolled 38 patients and divided them into two groups which 19 patients on CAD with type-2 diabetes mellitus and 19 patients without diabetes mellitus. Serum HMGB-1 levels in CAD with type-2 diabetes mellitus were increased significantly (p = 0.049) and not significantly decreased in CAD without type-2 diabetes mellitus (p = 0.480). The HMGB-1 level was not significantly different between the two groups (p = 0.210).


HMGB-1 levels after providing atorvastatin in CAD with type-2 diabetes mellitus increased significantly, meanwhile, in CAD without type-2 diabetes mellitus did not decrease significantly. The HMGB-1 level was not significantly different between the two groups. Longer time and more point for the collected sample needed for further research.

Corresponding author: Suharjono, Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Airlangga, Surabaya, East Java, Indonesia, E-mail:

Funding source: Tahir Professorship


Gratitude is due to the Director of Dr. Soetomo General Hospital, the Head of the Cardiology Room of Dr. Soetomo General Hospital, all patient and Tahir Professorship.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The local Institutional Review Board deemed the study exempt from review.


1. Sanchis-Gomar, F, Perez-Quilis, C, Leischik, R, Lucia, A. Epidemiology of coronary heart disease and acute coronary syndrome. Ann Transl Med 2016;4:256. in Google Scholar PubMed PubMed Central

2. Elhadd, TA, Al-Amoudi, AA, Alzahrani, AS. Epidemiology, clinical and complications profile of diabetes in Saudi Arabia: a review. Ann Saudi Med 2007;156:295–310.10.4103/0256-4947.51484Search in Google Scholar

3. Al-Habib, KF, Sulaiman, K, Al-Motarreb, A, Almahmeed, W, Asaad, N, Amin, H, et al.. Baseline characteristics, management practices, and long-term outcomes of middle eastern patients in the second Gulf Registry of acute coronary events (Gulf RACE-2). Ann Saudi Med 2012;32:9–18. in Google Scholar PubMed PubMed Central

4. Suzuki, LA, Poot, M, Gerrity, RG, Bornfeldt, KE. Diabetes Accelerates smooth muscle Accumulation in lesions of atherosclerosis: lack of direct growth-promoting effects of high glucose levels Diabetes 2001;50:851–60. in Google Scholar PubMed

5. Lim, SY. Role of statins in coronary artery disease Chonnam Med J 2013 49:1–6. in Google Scholar PubMed PubMed Central

6. Stancu, C, Sima, A. Statins: mechanism of action and effects J Cell Mol Med 2001;5:378–87. in Google Scholar PubMed PubMed Central

7. Barakat, L, Jayyousi, A, Bener, A, Zuby, B, Zirie, M. Comparison of efficacy and safety of rosuvastatin, atorvastatin and pravastatin among dyslipidemic diabetic patients. Hindawi Publishing Corporation ISRN Pharmacology; 2013:1–7 pp.10.1155/2013/146579Search in Google Scholar PubMed PubMed Central

8. Schaefer, EJ, McNamara, JR, Tayler, T, Daly, JA, Gleason, JL, Seman, LJ, Ferrari, A, et al.. Comparisons of effects of statins (atorvastatin, Fluvastatin, lovastatin, pravastatin, and simvastatin) on Fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects. Am J Cardiol 2004;93:31–9. in Google Scholar PubMed

9. Takazakura, A, Sakurai, M, Bando, Y, Misu, H, Takeshita, Y, Kita, Y, et al.. Renoprotective effects of atorvastatin compared with pravastatin on progression of early diabetic nephropathy. J Diabetes Investig 2015;6:346–53. in Google Scholar PubMed PubMed Central

10. Athyros, VG, Mikhailidis, DP, Papageorgiou, AA, Symeonidis, AN, Pehlivanidis, AN, Bouloukos, VI, et al.. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup Analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J Clin Pathol 2004;57:728–34. in Google Scholar PubMed PubMed Central

11. Shepherd, J, Kastelein, JJ, Bittner, V, Deedwania, P, Breazna, A, Dobson, S, et al.. Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (treating to new targets) study. J Am Coll Cardiol 2008;51:1448–1454. in Google Scholar PubMed

12. Van de Ree, MA, Huisman, MV, Princen, HM, Meinders, AE, Kluft, C. Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus. Atherosclerosis 2003;166:129–35. in Google Scholar

13. Hashimoto, T, Ishii, J, Kitagawa, F, Yamada, S, Hattori, K, Okumura, M, et al.. Circulating high-mobility group box 1 and cardiovascular mortality in unstable Angina and non-ST-segment elevation myocardial infarction. Atherosclerosis 2012;221:490–5. in Google Scholar PubMed

14. Andrassy, M, Volz, HC, Schuessler, A, Gitsioudis, G, Hofmann, N, et al.. HMGB1 is associated with Atherosclerotic plaque composition and burden in patients with stable coronary artery disease. PloS One 2012;7:e52081. in Google Scholar PubMed PubMed Central

15. Wu, H, Chen, Z, Xie, J, Kang, LN, Wang, L, Xu, B. High mobility group box-1: a missing link between diabetes and its complications. Hindawi Publishing Corporation Mediat Inflamm; 2016:1–11 pp.10.1155/2016/3896147Search in Google Scholar PubMed PubMed Central

16. Giallauria, F, Cirillo, P, Lucci, R, Pacileo, M, D’Agostino, M, Maietta, P, et al... Autonomic dysfunction is associated with high mobility group box-1 levels in patients after acute myocardial infarction. Atherosclerosis. 2010;208:280. in Google Scholar PubMed PubMed Central

17. Wang, L, Zhang, X, Liu, L, Yang, R, Cui, L, Li, M. Atorvastatin Protects rat brains against permanent focal ischemia and downregulates HMGB1, HMGB1 receptors (RAGE and TLR4), NF-kappaB expression. Neurosci Lett 2010;471:152–6. in Google Scholar PubMed

18. Zhao, H, Zhang, J, Yu, J. HMGB-1 as a potential target for the treatment of diabetic Retinopathy. Med Sci Monit 2015;21:3062–7. in Google Scholar PubMed PubMed Central

19. Yao, Y, Guo, D, Yang, S, Jin, Y, He, L, Chen, J, et al.. HMGB1 gene polymorphism is associated with hypertension in Han Chinese population. Clin Exp Hypertens 2015;37:166–71. in Google Scholar PubMed

20. Haraba, R, Uyy, E, Suica, VI, Ivan, L, Antohe, F. Fluvastatin reduces the high mobility group box 1 protein expression in hyperlipidemia. Int J Cardiol 2011;150:105–7. in Google Scholar PubMed

21. Smith, SCJr, Feldman, TE, Hirshfeld, JWJr, Jacobs, AK, Kern, MJ, King, SB3rd, et al.. American college of Cardiology/American heart association task Force on practice Guidelines; ACC/AHA/SCAI writing committee to update the 2001 Guidelines for percutaneous coronary intervention. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American college of Cardiology/American heart association task Force on practice Guidelines (ACC/AHA/SCAI writing committee to update the 2001 Guidelines for percutaneous coronary intervention). J Am Coll Cardiol 2006;47:e1–121. in Google Scholar PubMed

22. Cheng, Y, Wang, D, Wang, B, Li, H, Xiong, J, Xu, S, et al.. HMGB1 translocation and release mediate cigarette smoke–induced pulmonary inflammation in mice through a TLR4/MyD88-dependent signaling pathway. Mol Biol Cell 2017; 28: 201–9. in Google Scholar

23. Taylor, OJ, Porter, ME, Reynolds, PR, Bikman, BT. HMGB-1 mediates sidestream cigarette smoke-induced metabolic disruption. FASEB J. 2016;30:734.4–734.4.Search in Google Scholar

Received: 2020-12-31
Accepted: 2021-04-08
Published Online: 2021-06-25

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