Atorvastatin reduces serum HMGB1 levels in patients with hyperlipidemia

Jin,Daoqun; Wu,Yongbo; Zhao,Lin; Guo,Jie; Zhang,Kai; Chen,Zhiqiang

doi:10.3892/etm.2012.732

Atorvastatin reduces serum HMGB1 levels in patients with hyperlipidemia

Authors:
- Daoqun Jin
- Yongbo Wu
- Lin Zhao
- Jie Guo
- Kai Zhang
- Zhiqiang Chen
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Affiliations: Department of Cardiology, Central Hospital of Huangshi, Huangshi, P.R. China
Published online on: October 1, 2012 https://doi.org/10.3892/etm.2012.732
Pages: 1124-1126

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Abstract

High mobility group box 1 protein (HMGB1) has been identified as a novel pro-inflammatory cytokine in coronary artery disease. This study investigated the effect of atorvastatin on serum HMGB1 levels in patients with hyperlipidemia. In 72 patients with hyperlipidemia, serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP) were compared with the levels in 32 control patients. In hyperlipidemic patients, serum HMGB1 levels were also determined by ELISA before and after a 3-month treatment of atorvastatin (20 mg/day). TC and LDL-C levels in the hyperlipidemic group (6.37±0.94 and 4.99±0.75 mmol/l, respectively) were significantly higher compared to those in the control group (4.34±0.89 and 2.57±0.82 mmol/l, respectively) (both P<0.05). Hs-CRP and HMGB1 levels in the hyperlipidemic group (3.91±1.06 mg/l and 5.42±1.56 ng/ml, respectively) were also significantly higher compared to those in the control group (1.53±0.45 mg/l and 2.11±0.95 ng/ml, respectively) (both P<0.05). After treatment with atorvasatin for three months, TC and LDL-C levels in the hyperlipidemic group were significantly decreased compared to those prior to treatment (TC, 4.67±0.89 vs. 6.37±0.94 mmol/l and LDL-C, 2.75±0.92 vs. 4.99±0.75 mmol/l, respectively) (both P<0.05). HMGB1 and hs-CRP levels in the hyperlipidemic group (3.07±1.24 ng/ml and 1.87±0.79 mg/l, respectively) were also significantly decreased compared to levels prior to treatment (5.42±1.56 ng/ml and 3.91±1.06 mg/l, respectively) (both P<0.05). Serum HMGB1 levels are increased in patients with hyperlipidemia which could be reduced by atorvastatin.

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1	Libby P, Ridker PM and Maseri A: Inflammation and atherosclerosis. Circulation. 105:1135–1143. 2002. View Article : Google Scholar : PubMed/NCBI
2	Hansson GK: Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 352:1685–1695. 2005. View Article : Google Scholar : PubMed/NCBI
3	Ingelsson E, Schaefer EJ, Contois JH, McNamara JR, Sullivan L, Keyes MJ, et al: Clinical utility of different lipid measures for prediction of heart disease in men and women. JAMA. 298:776–785. 2007. View Article : Google Scholar : PubMed/NCBI
4	Siasos G, Tousoulis D, Oikonomou E, Zaromitidou M, Stefanadis C and Papavassiliou AG: Inflammatory markers in hyperlipidemia: from experimental models to clinical practice. Curr Pharm Des. 17:4132–4146. 2011. View Article : Google Scholar : PubMed/NCBI
5	Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, et al: HMG-1 as a late mediator of endotoxin lethality in mice. Science. 285:248–251. 1999. View Article : Google Scholar : PubMed/NCBI
6	Scaffidi P, Misteli T and Bianchi ME: Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 418:191–195. 2002. View Article : Google Scholar : PubMed/NCBI
7	Yan XX, Lu L, Peng WH, Wang LJ, Zhang Q, Zhang RY, et al: Increased serum HMGB1 level is associated with coronary artery disease in nondiabetic and type 2 diabetic patients. Atherosclerosis. 205:544–548. 2009. View Article : Google Scholar : PubMed/NCBI
8	Hu X, Jiang H, Bai Q, Zhou X, Xu C, Lu Z, et al: Increased serum HMGB1 is related to the severity of coronary artery stenosis. Clin Chim Acta. 406:139–142. 2009. View Article : Google Scholar : PubMed/NCBI
9	Ding HS and Yang J: High mobility group box-1 and cardiovascular diseases. Saudi Med J. 31:486–489. 2010.PubMed/NCBI
10	Kohno T, Anzai T, Naito K, Miyasho T, Okamoto K, Yokota H, et al: Role of high-mobility group box 1 protein in post-infarction healing process and left ventricular remodelling. Cardiovasc Res. 81:565–573. 2009. View Article : Google Scholar : PubMed/NCBI
11	Haraba R, Suica VI, Uyy E, Ivan L and Antohe F: Hyperlipidemia stimulates the extracellular release of the nuclear high mobility group box 1 protein. Cell Tissue Res. 346:361–368. 2011. View Article : Google Scholar : PubMed/NCBI
12	Kalinina N, Agrotis A, Antropova Y, DiVitto G, Kanellakis P, Kostolias G, et al: Increased expression of the DNA binding cytokine HMGB1 in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 24:2320–2325. 2004. View Article : Google Scholar : PubMed/NCBI
13	Inoue K, Kawahara KI, Krishna K, Ando K, Mitsudo K, Nobuyoshi M and Maruyama I: HMGB1 expression by activated vascular smooth muscle cells in advanced human atherosclerosis plaques. Cardiovasc Pathol. 16:136–143. 2007. View Article : Google Scholar : PubMed/NCBI
14	Niccoli G, Biasucci LM, Biscione, Fusco B, Porto I, Leone AM, et al: Independent prognostic value of C-reactive protein and coronary artery disease extent in patients affected by unstable angina. Atherosclerosis. 196:779–785. 2008. View Article : Google Scholar : PubMed/NCBI
15	Arroyo-Espliguero R, Avanzas P, Quiles J and Kaski JC: Predictive value of coronary artery stenoses and C-reactive protein levels in patients with stable coronary artery disease. Atherosclerosis. 204:239–243. 2009. View Article : Google Scholar : PubMed/NCBI
16	Musial J, Undas A, Gajewski P, Jankowski M, Sydor W and Szczeklik A: Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia. Int J Cardiol. 77:247–253. 2001. View Article : Google Scholar : PubMed/NCBI
17	Ascer E, Bertolami MC, Venturinelli ML, Buccheri V, Souza J, Nicolau JC, et al: Atorvastatin reduces proinflammatory markers in hypercholesterolemic patients. Atherosclerosis. 177:161–166. 2004. View Article : Google Scholar : PubMed/NCBI
18	Hu X, Fu W and Jiang H: HMGB1: A potential therapeutic target for myocardial ischemia and reperfusion injury. Int J Cardiol. 155:489. 2012. View Article : Google Scholar : PubMed/NCBI
19	Wang L, Zhang X, Liu L, Yang R, Cui L and Li M: Atorvastatin protects rat brains against permanent focal ischemia and downregulates HMGB1, HMGB1 receptors (RAGE and TLR4), NF-kappaB expression. Neurosci Lett. 471:152–156. 2010. View Article : Google Scholar : PubMed/NCBI
20	Yang J, Huang C, Yang J, Jiang H and Ding J: Statins attenuate high mobility group box-1 protein-induced vascular endothelial activation: a key role for TLR4/NF-κB signaling pathway. Mol Cell Biochem. 345:189–195. 2010.PubMed/NCBI
21	Blumenthal RS and Boltlmore MD: Statins: effective antiathero-sclerotic therapy. Am Heart J. 139:577–583. 2000. View Article : Google Scholar : PubMed/NCBI