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vol. 14
Experimental research

Effects and potential mechanism of atorvastatin treatment on Lp-PLA2 in rats with dyslipidemia

Dongdan Zheng, Anping Cai, Rulin Xu, Zhuocheng Mai, Yingling Zhou, Fanfang Zeng, Liwen Li, Weiyi Mai

Arch Med Sci 2018; 14, 3: 629–634
Online publish date: 2017/08/10
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The effects of statins on lipoprotein-associated phospholipase A2 (Lp-PLA2) are controversial, and the present study aimed to investigate whether atorvastatin could reduce Lp-PLA2 in rats with dyslipidemia.

Material and methods
A high-fat and high-cholesterol diet was prescribed to produce a dyslipidemia model. Thereafter, low-dose atorvastatin (5 mg/kg/day), high-dose atorvastatin (20 mg/kg/day) or saline (without-treatment group) was prescribed for 14 days. At 6 weeks after dyslipidemia model establishment and 14 days of atorvastatin treatment, fasting venous blood was drawn for biochemical analysis. Between-group differences and Pearson correlation analysis were conducted.

Compared to the normal-control group, fasting plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly increased in dyslipidemia groups, while plasma nitric oxide (NO) levels were significantly decreased with attendant elevation of plasma C-reactive protein (CRP) and rho-associated kinase 1 (ROCK1) levels (p < 0.05). At 14 days of atorvastatin treatment, compared to the without-treatment group, plasma levels of TC and LDL-C in the high-dose group were significantly reduced (p < 0.05); and compared to low-dose and without-treatment groups, NO up-regulation (1.8 ±1.1 µmol/l), and CRP (–0.8 ±0.4 ng/ml), ROCK1 (–124 ±65 mmol/l) and Lp-PLA2 (–3.8 ±1.2 ng/ml) reduction were more significant in the high-dose group (p < 0.05). Pearson correlation analysis showed that TC (r = 0.365), LDL-C (r = 0.472), CRP (r = 0.501) and ROCK1 (r = 0.675) were positively correlated with Lp-PLA2, while NO (r = –0.378) and atorvastatin (r = –0.511) were negatively correlated with Lp-PLA2.

Atorvastatin treatment is beneficial for reducing the Lp-PLA2 level in rats with dyslipidemia, which may be related to reduced ROCK1 expression in a dose-dependent manner.


dyslipidemia, endothelial dysfunction, statins, lipoprotein-associated phospholipase A2

Johnson ML, Pietz K, Battleman DS, Beyth RJ. Prevalence of comorbid hypertension and dyslipidemia and associated cardiovascular disease. Am J Manag Care 2004; 10: 926-32.
Mahdavi H, Kim JB, Safarpour S, Tien DA, Navab M. Dyslipidemia and cardiovascular diseases. Curr Opin Lipidol 2009; 20: 157-8.
Siri-Tarino PW, Krauss RM. Diet, lipids, and cardiovascular disease. Curr Opin Lipidol 2016; 27: 323-8.
Cheng HG, Patel BS, Martin SS, et al. Effect of comprehensive cardiovascular disease risk management on longitudinal changes in carotid artery intima-media thickness in a community-based prevention clinic. Arch Med Sci 2016; 12: 728-35.
von SBJ, Reinhard H, Hansen TW, et al. Markers of inflammation and endothelial dysfunction are associated with incident cardiovascular disease, all-cause mortality, and progression of coronary calcification in type 2 diabetic patients with microalbuminuria. J Diabetes Complications 2016; 30: 248-55.
Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000; 87: 840-4.
Heitzer T, Schlinzig T, Krohn K, Meinertz T, Münzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001; 104: 2673-8.
Vittos O, Toana B, Vittos A, Moldoveanu E. Lipoprotein-associated phospholipase A2 (Lp-PLA2): a review of its role and significance as a cardiovascular biomarker. Biomarkers 2012; 17: 289-302.
Sudhir K. Clinical review: Lipoprotein-associated phospholipase A2, a novel inflammatory biomarker and independent risk predictor for cardiovascular disease.
J Clin Endocrinol Metab 2005; 90: 3100-5.
Zheng D, Zeng F, Cai A, et al. Baseline elevated Lp-PLA2 is associated with increased risk for re-stenosis after stent placement. Lipids Health Dis 2014; 13: 41.
Colley KJ, Wolfert RL, Cobble ME. Lipoprotein associated phospholipase A(2): role in atherosclerosis and utility as a biomarker for cardiovascular risk. EPMA J 2011; 2: 27-38.
Wilensky RL, Macphee CH. Lipoprotein-associated phospholipase A(2) and atherosclerosis. Curr Opin Lipidol 2009; 20: 415-20.
Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med 2008; 14: 37-44.
Epstein M, Campese VM. Pleiotropic effects of 3-hydroxy- 3-methylglutaryl coenzyme a reductase inhibitors on renal function. Am J Kidney Dis 2005; 45: 2-14.
Huang C, Cen C, Wang C, Zhan H, Ding X. Synergistic effects of colchicine combined with atorvastatin in rats with hyperlipidemia. Lipids Health Dis 2014; 13: 67.
Zheng D, Liang Q, Zeng F, et al. Atorvastatin protects endo­thelium by decreasing asymmetric dimethylarginine in dyslipidemia rats. Lipids Health Dis 2015; 14: 41.
Cai A, Qiu R, Li L, et al. Atorvastatin treatment of rats with ischemia-reperfusion injury improves adipose-derived mesenchymal stem cell migration and survival via the SDF-1/CXCR-4 axis. PLoS One 2013; 8: e79100.
Ghomari-Boukhatem H, Bouchouicha A, Mekki K, Chenni K, Belhadj M, Bouchenak M. Blood pressure, dyslipidemia and inflammatory factors are related to body mass index in scholar adolescents. Arch Med Sci 2017; 13: 46-52.
Sawada N, Liao JK. Rho/Rho-associated coiled-coil forming kinase pathway as therapeutic targets for statins in atherosclerosis. Antioxid Redox Signal 2014; 20: 1251-67.
Cai A, Li L, Zhou Y. Pathophysiological effects of RhoA and Rho-associated kinase on cardiovascular system. J Hypertens 2016; 34: 3-10.
Jasińska-Stroschein M, Owczarek J, Sołtysiak U, Orszulak-Michalak D. Rosuvastatin intensifies the beneficial effects of rho-kinase inhibitor in reversal of monocrotaline-induced pulmonary hypertension. Arch Med Sci 2016; 12: 898-905.
Rikitake Y, Liao JK. Rho GTPases, statins, and nitric oxide. Circ Res 2005; 97: 1232-5.
Soga J, Noma K, Hata T, et al. Rho-associated kinase activity, endothelial function, and cardiovascular risk factors. Arterioscler Thromb Vasc Biol 2011; 31: 2353-9.
White HD, Simes J, Stewart RA, et al. Changes in lipoprotein-associated phospholipase A2 activity predict coronary events and partly account for the treatment effect of pravastatin: results from the Long-Term Intervention with Pravastatin in Ischemic Disease study. J Am Heart Assoc 2013; 2: e000360.
Albert MA, Glynn RJ, Wolfert RL, Ridker PM. The effect of statin therapy on lipoprotein associated phospholipase A2 levels. Atherosclerosis 2005; 182: 193-8.
Nohria A, Prsic A, Liu PY, et al. Statins inhibit Rho kinase activity in patients with atherosclerosis. Atherosclerosis 2009; 205: 517-21.
Garg PK, McClelland RL, Jenny NS, et al. Association of lipoprotein-associated phospholipase A(2) and endothelial function in the Multi-Ethnic Study of Atherosclerosis (MESA). Vasc Med 2011; 16: 247-52.
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