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Open Access 01-12-2014 | Original Research Article

Assessment of the Prophylactic Role of Aspirin and/or Clopidogrel on Experimentally Induced Acute Myocardial Infarction in Hypercholesterolemic Rats

Authors: Adham R. Mohamed, Wessam F. El-Hadidy, Hazem F. Mannaa

Published in: Drugs in R&D | Issue 4/2014

Abstract

Introduction

Hyperlipidemia is a risk factor for cardiovascular diseases such as acute infarction. Inflammation and platelet activation are critical phenomena in acute myocardial infarction (AMI).

Aim

The aim of the study was to assess potential protective effects of aspirin and/or clopidogrel on AMI in hypercholesterolemic rats.

Methods

Forty adult male Wistar rats were divided into five groups (eight rats in each). Group I included normal healthy rats. The other 32 rats were subjected to induction of hypercholesterolemia by high-fat diet for 3 weeks, followed by induction of AMI by subcutaneous injections of isoproterenol (85 mg/kg/day, for 2 days). Rats were divided into the following groups: group II, rats with induced hypercholesterolemia and AMI; group III, hypercholesterolemic rats that received aspirin 30 mg/kg/day orally for 7 days before induction of AMI; group IV, hypercholesterolemic rats that received clopidogrel 10 mg/kg/day orally for 7 days before induction of AMI; and group V, hypercholesterolemic rats treated with both aspirin and clopidogrel in the same doses for 7 days before induction of AMI. Serum levels of pentraxin 3 (PTX3), transforming growth factor-β1 (TGF-β1), creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol and triglycerides were estimated in all rats.

Results

Isoproterenol-induced AMI in hypercholesterolemic rats was associated with an increase in serum levels of PTX3, TGF-β1, CK and LDH. Aspirin and/or clopidogrel pretreatment for 1 week led to a reduction of their levels as compared with non-treated rats. However, the reduction caused by combination of aspirin and clopidogrel was more than that caused by each drug separately.

Conclusion

Combination of aspirin and clopidogrel could be a therapeutic option for hypercholesterolemic patients to attenuate the complex vascular inflammatory process which is a key step in the setting of AMI.

Roffi M, Brindle M, Robbins M, Mukherjee D. Current perspectives on coronary revascularization in diabetic patients. Indian Heart J. 2007;59:124–36.PubMed

Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105:1135–43.PubMedCrossRef

Kume N, Mitsuoka H, Hayashida K, Tanaka M. Pentraxin 3 as a biomarker for acute coronary syndrome: comparison with biomarkers for cardiac damage. J Cardiol. 2011;58(1):38–45.PubMedCrossRef

Norata GD, Garlanda C, Catapano AL. The long pentraxin PTX3: a modulator of the immunoinflammatory response in atherosclerosis and cardiovascular diseases. Trends Cardiovasc Med. 2010;20(2):35–40.PubMedCrossRef

Maugeri N, Rovere P, Slavich M, et al. Early and transient release of leukocyte pentraxin 3 during acute myocardial infarction. J Immunol. 2011;187(2):970–9.PubMedCrossRef

Gurbel PA, Tantry US. The rationale for and comparisons of different antiplatelet treatment in acute coronary syndrome. J Interv Cardiol. 2008;21(Suppl (1)):S10–7.PubMedCrossRef

Garlanda C, Bottazi B, Bastone A. Pentraxins at the cross roads between innate immunity, inflammation, matrix deposition. Annu Rev Immunol. 2005;23:337–66.PubMedCrossRef

Muhlestein JB. Effect of antiplatelet therapy on inflammatory markers in atherothrombotic patients. Thromb Haemost. 2010;103(1):71–82.PubMedCrossRef

Srinivasan K, Viswanad B, Lydia A, Kaul CL, Romarao P. Combination of high-fat diet-fed and low-dose streptozotocin—treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res. 2005;52(4):313–20.PubMedCrossRef

10.

Zaitone SA, Abo-Gresha NM. Rosuvastatin promotes angiogenesis and reverse isoproterenol- induced acute myocardial infarction in rats: role of iNOS and VEGF. Eur J Pharmacol. 2012;691(1–3):134–42.PubMedCrossRef

11.

Fu Y, Wang Z, Chen WL, Moore PK, Zhu YZ. Cardioprotective effects of nitric-oxide aspirin in myocardial ischemia—reperfused rats. Am J Physiol Heart Circ Physiol. 2007;293(3):545–52.CrossRef

12.

Dhanjal TS, Medina RA, Leem J, Clark JE, South Worth R, Curtis MJ. Trapped platelets activated in ischemia initiate ventricular fibrillation. Circ Arrhythm Electrophysiol. 2013;6(5):995–1001.PubMedCrossRef

13.

Okutani D, Han B, Mura M, Waddell TK, Keshavjee S, Liu M. High-volume ventilation induces pentraxin 3 expression in multiple acute lung injury models in rats. Am J Physiol Lung Cell Mol Physiol. 2007;292(1):L144–53.PubMedCrossRef

14.

Varedi M, Jeschke MG, Englander EW, Herndon DN, Barrow RE. Serum TGF-beta in thermally injured rats. Shock. 2001;6(5):380–2.CrossRef

15.

Bishop C, Chu TM, Shihabi ZK. Single stable reagent for creatine kinase assay. Clin Chem. 1971;17(6):548–50.PubMed

16.

Babson AL, Babson SR. Kinetic calorimetric measurement of serum lactate dehydrogenase activity. Clin Chem. 1973;19(7):766–9.PubMed

17.

Allain CC, Poon LS, Chan CSG, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem. 1974;20:470–5.PubMed

18.

Bucolo G, David H. Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem. 1973;19(5):476–82.PubMed

19.

Suzuki S, Takeishi Y, Niizeki T, et al. Pentraxin 3, a new marker for vascular inflammation, predicts adverse clinical outcomes in patients with heart failure. Am Heart J. 2008;155(1):75–81.PubMedCrossRef

20.

Salio M, Chimenti S, De Angelis N, et al. Cardioprotective function of the long pentraxin PTX3 in acute myocardial infarction. Circulation. 2008;117(8):1055–64.PubMedCrossRef

21.

Kunes P, Holubcova Z, Kolackova M, Krejisek J. Pentraxin 3 (PTX3): an endogenous modulator of the inflammatory response. Mediators Inflamm. 2012;2012:920517.PubMedCentralPubMedCrossRef

22.

Ustundag M, Orak M, Gulog C, Sayhan MB, Alyano O, Kale E. Comparative diagnostic accuracy of serum levels of neutrophil activating peptide-2 and pentraxin 3 versus troponin-I in acute coronary syndrome. Anadolu Kardiyol Derg. 2011;11(7):588–94.PubMed

23.

Barbati E, Specchia C, Villella M, et al. Influence of pentraxin3 (PTX3) genetic variants on myocardial infarction risk and PTX3 plasma levels. Plos One. 2012;7(12):e 53030.CrossRef

24.

Kimura S, Inagaki H, Haraguchi G, et al. Relationships of elevated systemic pentraxin 3 levels with high risk coronary plaque components and impaired myocardial perfusion after percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction. Circ J. 2013;78(1):159–69.PubMed

25.

Eggers KM, Armstrong PW, Califf RM, et al. Clinical and prognostic implications of circulating pentraxin 3 levels in non-ST-elevation acute coronary syndrome. Clin Biochem. 2013;46(16–17):1655–9.PubMedCrossRef

26.

Steinhubl SR, Badimon JJ, Bhatt DL, Herbert JM, Lüscher TF. Clinical evidence for anti-inflammatory effects of antiplatelet therapy in patients with atherothrombotic disease. Vasc Med. 2007;12(2):113–22.PubMedCrossRef

27.

Terpening C. An appraisal of dual antiplatelet therapy with clopidogrel and aspirin for prevention of cardiovascular events. J Am Board Fam Med. 2009;22:51–6.PubMedCrossRef

28.

Yamasaki T, Koizumi T, Tamaki T, et al. Differing behavior of plasma pentraxin 3 and high-sensitive CRP at the very onset of myocardial infarction with ST-segment elevation. Angiol. 2013;1(1):1–5.CrossRef

29.

Helseth R, Solheim S, Opstad T, Hoffmann P, Arnesen H, Seljeflot I. The time profile of pentraxin 3 in patients with acute ST-elevation myocardial infarction and stable angina pectoris undergoing percutaneous coronary intervention. Mediators Inflamm. 2014;2014:608414.PubMedCentralPubMedCrossRef

30.

Herder C, Peeters W, Zierer A, de Kleijn DP, Moll FL, Roden M. TGF-β1 content in atherosclerotic plaques, TGF-β1 serum concentrations and incident coronary events. Eur J Clin Invest. 2012;42(3):329–37.PubMedCrossRef

31.

Najar RA, Ghaderian SM, Panah AS. Association of transforming growth factor–β1 gene polymorphism with genetic susceptibility to acute myocardial infarction. Am J Med Sci. 2011;342(5):365–70.PubMedCrossRef

32.

Chen C, Lei W, Chen W, et al. Serum TGF-β1 and SMAD3 levels are closely associated with coronary artery disease. BMC Cardiovas Disord. 2014;14:18.CrossRef

33.

Hudzik B, Szkodzinski J, Danikiewicz K, et al. Effect of omeperazole on the concentration of interleukin-6 and transforming growth factor–β1 in patients receiving dual antiplatelet therapy after percutaneous coronary intervention. Eur Cytokine Netw. 2010;21(4):257–63.PubMed

34.

Lobo HG, Fereira NL, Sousa RB, Carvalho ER, Lobo PL. Experimental model of myocardial infarction induced by isoproterenol in rats. Rev Bras Circ Cardiovasc. 2011;26(3):469–76.CrossRef

35.

Yue-tao L, Hong-mei J, Xing-chang C, Hong-wu Z, Zhong-mei Z. The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on tissue targeted metabonomics. Mol Biosyst. 2013;9:2823–34.CrossRef

36.

Wang CH, Yang J, Shen ZJ, Fang Q, Zhang SY, Fan ZJ. Effect of duration of clopidogrel use on clinical follow-up outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. Zhonghua Yi Xue Za Zhi. 2010;90(24):1682–5.PubMed

37.

Acharji S, Lakshmanodoss U, Rudzinski W, Stapleton D, Kaluski E. Use of antiplatelet agents in patients with atherosclerotic diseases. Postgrad Med. 2013;125(5):19–30.PubMedCrossRef

Title: Assessment of the Prophylactic Role of Aspirin and/or Clopidogrel on Experimentally Induced Acute Myocardial Infarction in Hypercholesterolemic Rats
Authors: Adham R. Mohamed
Wessam F. El-Hadidy
Hazem F. Mannaa
Publication date: 01-12-2014
Publisher: Springer International Publishing
Published in: Drugs in R&D / Issue 4/2014
Print ISSN: 1174-5886
Electronic ISSN: 1179-6901
DOI: https://doi.org/10.1007/s40268-014-0059-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Assessment of the Prophylactic Role of Aspirin and/or Clopidogrel on Experimentally Induced Acute Myocardial Infarction in Hypercholesterolemic Rats

Abstract

Introduction

Aim

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Aim

Methods

Results

Conclusion

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