The strong association among the risk of coronary artery diseases (CAD), high levels of LDL-C and low levels of HDLC is well established. Hyperhomocysteinaemia (HHcy) is an independent risk factor for cardiovascular disease (CVD) and causes endothelial dysfunction, a hallmark of atherosclerosis. In this study, we ascertained the influence of statins on the atherogenic index, as an indicator and a significant adjunct for predicting atherosclerosis in hyperhomocysteinaemic male Wistar albino rats. For 4 weeks, the animals were fed with one of the following diets (Mucedola SRL., Milan, Italy): standard rodent chow; a diet enriched in methionine with no deficiency in B vitamins or a diet enriched in methio-nine and deficient in B vitamins. The animals were simultaneously exposed to a pharmacology treatment with atorvastatin at dose of 3 mg/kg/day i.p. or simvastatin, at dose of 5 mg/kg/day i.p. We measured weight gain, food intake, and FER and determined the concentrations of biochemical parameters of dyslipidaemia (TC, TGs, LDL-C, VLDL-C, and HDL-C), AI, and CRR. A histopathological examination was conducted on portions of the right and left liver lobes from each animal. A connection between Hhcy and dyslipidaemia was indicated by the findings of biochemical and histological analyses, suggesting that Hhcy was a pro-atherogenic state. An improvement in the lipid profile along with a decrease in the atherogenic index by statins suggests that atorvastatin and simvastatin could be useful antiatherogenic agents, with protective activities during hyperhomocysteinaemia.
5. Castelli WP. Cholesterol and lipids in the risk of coronary artery disease-the Framingham Heart study. Can J Cardiol. 1988;4:5–10
6. Hokanson JE Austin MA. Plasma triglyceride level is a risk factor to cardio vascular disease independent of high density lipoprotein cholesterol level: a meta analysis of population based prospective studies. J Cardiovasc Risk. 1996;3:213–219.
7. Guerin M Legoff W Lassel TS VanTol A Steiner G Chapman MJ. Proatherogenic role of elevated CE transfer from HDL to VLDL and dense LDL in type 2 diabetics. Arterioscler Thromb Vasc Biol. 2001;21:282–287.
8. Gaziano JM Henne kens CH O’Donnell CJ Breslow JL Buring JE. Fasting triglycerides high density lipo-protein and risk of myocardial infarction. Circulation. 1997;96:2520–2525.
9. Dobiasova M Frohlich J. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apo B-lipoprotein-depleted plasma. (FERHDL) Clin Biochem. 2001;34:583–588.
10. Jakubowski H. Proofreading in vivo. Editing of homo-cysteine by aminoacyl-tRNA synthetases in Escherichia coli. J Biol Chem. 1995;270:17672–17673.
11. Jakubowski H. Metabolism of homocysteine thiolac-tone in human cell cultures. Possible mechanism for pathological consequences of elevated homocysteine levels. J Biol Chem. 1997;272:1935–1942.
12. Jakubowski H. Synthesis of homocysteine thiolactone in normal and malignant cells. In: Rosenberg IH Graham I Ueland PM Refsum H editors. Homocysteine metabolism: from basic science to clinical medicine. Norwell: Kluwer Academic Publishers; 1997. pp. 157–165.
13. Jakubowski H. Protein homocysteinylation: possible mechanism underlying pathological consequences of elevated homocysteine levels. Faseb J. 1999;13:2277–2283.
14. Jakubowski H. Calcium-dependent human serum homo-cysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J Biol Chem. 2000;275:3957–3962. doi: 10.1074/jbc.275.6.3957.
15. Jakubowski H. The determination of homocysteinethiolactone in biological samples. Anal Biochem. 2002;308:112–119. doi: 10.1016/S0003-2697(02)00224-5.
16. Eriksson M. [Statins have other beneficial properties besides their cholesterol lowering effect]. Lakartidningen. 1998 Aug 26;95(35):3670-2. Review. Swedish. PubMed PMID: 9748780
17. Demacher M Hijamaus A. A study of the use of polyethylene glycol in estimating cholesterol. Clin Chem. 1980; 26:1775.
18. Foster L Dunn R. Stable reagens for the determination os serum triglycerides by a colorimetric Hantzch condensation method. J Clin Chem 1973; 19:338.
19. Roberts WC. The Friedewald-Levy-Fredrickson formula for calculating low-density lipoprotein cholesterol the basis for lipid-lowering therapy. Am J Cardiol. 1988;62:345–6.
20. Zlatkis A Zak B Boyle A. A new method for the direct determination of cholesterol. J lab Clin Med. 1953;41:486–486
21. Niroumand S Khajedaluee M Khadem-Rezaiyan M et al. Atherogenic Index of Plasma (AIP): A marker of cardiovascular disease. Medical Journal of the Islamic Republic of Iran. 2015;29:240.
22. Brunt EM Tiniakos DG. Alcoholic and nonalcoholic fatty liver disease. In: Odze RD Goldblum JR eds editors. Surgical Pathology of the GI Tract Liver Biliary Tract and Pancreas. 2nd ed. Philadelphia: Elsevier; 2009. pp. 1007–1014
23. Kleiner DE Brunt EM Van Natta M Behling C Contos MJ Cummings OW Ferrell LD Liu YC Torbenson MS Unalp-Arida A et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321.
24. Nikolic T Zivkovic V Srejovic I Stojic I Jeremic N Jeremic J Radonjic K Stankovic S Obrenovic R Djuric D Jakovljevic V. Effects of atorvastatin and simvastatin on oxidative stress in diet-induced hyperhomocysteinemia in Wistar albino rats: a comparative study. Mol Cell Biochem. 2017 Jun 15. doi: 10.1007/s11010-017-3099-5.
25. Brown DJ. New guidelines for low-density lipoprotein levels fron the National Cholesterol Education Program (NCEP): a 2004 update. Prog Cardiovasc Nurs. 2004 Fall;19(4):165. PubMed PMID: 15539979.
26. King A. Cardioprotective effects of HDL cholesterol called into question. Nature Reviews Cardiology. 2012;9 [PubMed]
27. Rekhter MD. How to evaluate plaque vulnerability in animal models of atherosclerosis? Cardiovascular research. 2002;54:36–41.
28. Bhandari U Pathan RA Kumar V Khanna N. Ameliorative role of atorvastatin on methionine-induced hyperhomcysteinemia and hematological changes in albino rats. Indian J Exp Biol. 2011: 132-9.
29. Matté C Stefanello FM Mackedanz V Pederzolli CD Lamers ML Dutra-Filho CS Dos Santos MF Wyse AT. Homocysteine induces oxidative stress inflammatory infiltration fibrosis and reduces glycogen/glycoprotein content in liver of rats. Int J Dev Neurosci. 2009; 27(4):337-44. 7.
30. Zhang R Ma J Xia M Zhu H Ling WH. Mild hyperhomocysteinemia Induced by feeding Rats Diets Rich in Methionine or Deficient in Folate Promotes Early Atherosclerotic Inflamammatory Processes. J Nutr. 2004: 825-30.
31. Ankur Rohilla M. U. Khan Razia Khanam. Cardioprotective potential of simvastatin in the hyperhomocysteinemic rat heart. J Adv Pharm Technol Res. 2012; 3(3): 193–198.
32. Rohilla A Ahmad A Khan MU Khanam R. A comparative study on the cardioprotective potential of atorvastatin and simvastatin in hyperhomocysteinemic rat hearts. Eur J Pharmacol. 2015;764:48-54.
33. Olszewski AJ McCully KS. Homocysteine content of lipoproteins in hypercholesterolemia. Atherosclerosis. 1991 May;88(1):61-8. PubMed PMID: 1878010.
34. Malik J Melenovsky V Wichterle D et al. Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidemia (fenofibrate versus atorvastatin trial-FAT). Cardiovasc Res 2001: 290-8. 12.
35. Luftjohann D Sigit IJ Locatelli S Bergmann VK. High-dose simvastatin (80mg/day) decreases plasma concentrations of total homocysteine in patients with hyper-cholesterolemia. Atherosclerosis. 2001: 265-6.