Download PDF
Drug Res (Stuttg) 2014; 64(11): 576-583
DOI: 10.1055/s-0033-1363230
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Effects of LDL and Oxidized LDL on Cardiac Function in Isoproterenol-induced Myocardial Infarction in Rat

A. Khorrami
1   Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
3   Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
S. Ghanbarzadeh
2   Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
3   Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
M. Ziaee
4   Young Research Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran
,
S. Arami
5   Pharmaceutical Biotechnology Department, Faculty of Pharmacy, Tabriz University Of Medical Sciences, Tabriz, Iran
,
S. Andalib
1   Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
N. Maleki-Dizaji
1   Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
A. Garjani
1   Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 07 September 2013

accepted 25 November 2013

Publication Date:
17 January 2014 (online)

Also available at
    Permissions and Reprints

Abstract

Background:

Notable discussions have been developed over the distinctive effects of LDL and oxidized LDL (OxLDL) on myocardial functions. The aim of the present study was to investigate the effects of OxLDL on electrocardiogram and hemodynamic parameters of rat’s heart in isoproterenol (ISO)-induced myocardial infarction (MI) model.

Method:

Male Wistar rats were allocated in to 6 groups and receive one of the 3 formulated diets (standard, cholesterol-rich and oxidized cholesterol-rich diets). After 14 weeks to induce MI, rats in 3 groups were received ISO (100 mg/kg) for 2 consecutive days subcutaneously. Lipid profiles, electrocardiogram patterns and hemodynamic parameters of all groups were investigated.

Results:

Serum levels of LDL, cholesterol and triglycerides were significantly higher in the fat-rich diet fed groups compared to control group (P<0.001). The ISO-treated rats showed a marked reduction in the R-amplitude, R–R interval, LVSP, left ventricular contractility (LVdP/dtmax) and relaxation (LVdP/dtmin) as well as severe elevation in ST-segment and LVEDP value compared to the respective normal rats. High serum level of OxLDL resulted in significant exacerbation in the destructive effects of ISO on R-amplitude, R–R interval, LVSP, left ventricular contractility (LVdP/dtmax), relaxation (LVdP/dtmin), ST-segment and LVEDP values. Additionally, heart to body weight ratio as an index of myocardial edematous was also increased significantly. However, changes in these parameters in rats fed with cholesterol-rich diet were not significant.

Conclusion:

Generally, results indicated that the effects of high OxLDL level on electrocardiogram and hemodynamic parameter after MI was more reliable than effects of high LDL level.

Key words

hypercholesterolemia - electrocardiogram - hemodynamic - ischemic heart
 

  • References

  • 1 Abdallah MH, Arnaout S, Karrowni W et al. The management of acute myocardial infarction in developing countries. International Journal of Cardiology 2006; 111: 189-194
    CrossrefPubMedGoogle Scholar
  • 2 Herlitz J, Hjalmarson Å, Swedberg K et al. The influence of early intervention in acute myocardial infarction on long-term mortality and morbidity as assessed in the Göteborg metoprolol trial. International Journal of Cardiology 1986; 10: 291-301
    CrossrefPubMedGoogle Scholar
  • 3 Vega G, Martínez S, Jiménez PA et al. Effect of Cardiovascular Risk Factors on Long-Term Morbidity and Mortality Following Acute Myocardial Infarction. Revista Española de Cardiología (English Edition) 2007; 60: 703-713
    CrossrefPubMedGoogle Scholar
  • 4 Gorog DA, Ahmed N, Davies GJ. Elevated plasma lipid peroxide levels in angina pectoris and myocardial infarction. Cardiovascular Pathology 2002; 11: 153-157
    CrossrefPubMedGoogle Scholar
  • 5 Karthikeyan G, Teo KK, Islam S et al. Lipid Profile, Plasma Apolipoproteins, and Risk of a First Myocardial Infarction Among Asians: An Analysis From the INTERHEART Study. Journal of the American College of Cardiology 2009; 53: 244-253
    CrossrefPubMedGoogle Scholar
  • 6 Kumar A, Biswas UK, Nagtilak S et al. Lipid ratio useful indicator in predicting risk of myocardial infarction in elderly normolipidemic patients: a report from a multi center study. Asian Pacific Journal of Tropical Disease 2011; 1: 123-126
    CrossrefPubMedGoogle Scholar
  • 7 Wright RS, Murphy JG, Bybee KA et al. Statin Lipid-Lowering Therapy for Acute Myocardial Infarction and Unstable Angina: Efficacy and Mechanism of Benefit. Mayo Clinic Proceedings 2002; 77: 1085-1092
    CrossrefPubMedGoogle Scholar
  • 8 Gómez M, Valle V, Arós F et al. Oxidized LDL, Lipoprotein (a), and Other Emergent Risk Factors in Acute Myocardial Infarction (FORTIAM Study). Revista Española de Cardiología (English Edition) 2009; 62: 373-382
    CrossrefPubMedGoogle Scholar
  • 9 Holvoet P, Jenny NS, Schreiner PJ et al. The relationship between oxidized LDL and other cardiovascular risk factors and subclinical CVD in different ethnic groups: The Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2007; 194: 245-252
    CrossrefPubMedGoogle Scholar
  • 10 Hulthe J. Antibodies to oxidized LDL in atherosclerosis development – clinical and animal studies. Clinica Chimica Acta 2004; 348: 1-8
    CrossrefPubMedGoogle Scholar
  • 11 Munteanu A, Zingg J-M. Cellular, molecular and clinical aspects of vitamin E on atherosclerosis prevention. Molecular Aspects of Medicine 2007; 28: 538-590
    CrossrefPubMedGoogle Scholar
  • 12 Nakajima K, Nakano T, Tanaka A. The oxidative modification hypothesis of atherosclerosis: The comparison of atherogenic effects on oxidized LDL and remnant lipoproteins in plasma. Clinica Chimica Acta 2006; 367: 36-47
    CrossrefPubMedGoogle Scholar
  • 13 Vasankari T, Ahotupa M, Toikka J et al. Oxidized LDL and thickness of carotid intima-media are associated with coronary atherosclerosis in middle-aged men: lower levels of oxidized LDL with statin therapy. Atherosclerosis 2001; 155: 403-412
    CrossrefPubMedGoogle Scholar
  • 14 Jones PJH. Dietary agents that target gastrointestinal and hepatic handling of bile acids and cholesterol. Journal of Clinical Lipidology 2008; 2: S4-S10
    PubMedGoogle Scholar
  • 15 Trautwein EA, Siddiqui A, Hayes KC. Characterization of the bile acid profile in developing male and female hamsters in response to dietary cholesterol challenge. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 1999; 124: 93-103
    CrossrefPubMedGoogle Scholar
  • 16 Martinez-Seara H, Róg T, Pasenkiewicz-Gierula M et al. Interplay of Unsaturated Phospholipids and Cholesterol in Membranes: Effect of the Double-Bond Position. Biophysical Journal 2008; 95: 3295-3305
    CrossrefPubMedGoogle Scholar
  • 17 Niki E. Lipid peroxidation: Physiological levels and dual biological effects. Free Radical Biology and Medicine 2009; 47: 469-484
    CrossrefPubMedGoogle Scholar
  • 18 Pulla Reddy AC, Lokesh BR. Dietary unsaturated fatty acids, vitamin E, curcumin and eugenol alter serum and liver lipid peroxidation in rats. Nutrition Research 1994; 14: 1423-1437
    CrossrefPubMedGoogle Scholar
  • 19 Spiteller G. Linoleic acid peroxidation – the dominant lipid peroxidation process in low density lipoprotein – and its relationship to chronic diseases. Chemistry and Physics of Lipids 1998; 95: 105-162
    CrossrefPubMedGoogle Scholar
  • 20 Hovenkamp E, Demonty I, Plat J et al. Biological effects of oxidized phytosterols: A review of the current knowledge. Progress in Lipid Research 2008; 47: 37-49
    CrossrefPubMedGoogle Scholar
  • 21 Leonarduzzi G, Sottero B, Poli G. Oxidized products of cholesterol: dietary and metabolic origin, and proatherosclerotic effects (review). The Journal of Nutritional Biochemistry 2002; 13: 700-710
    CrossrefPubMedGoogle Scholar
  • 22 Lu Y-F, Lo Y-C. Effect of deep frying oil given with and without dietary cholesterol on lipid metabolism in rats. Nutrition Research 1995; 15: 1783-1792
    CrossrefPubMedGoogle Scholar
  • 23 Otaegui-Arrazola A, Menéndez-Carreño M, Ansorena D et al. Oxysterols: A world to explore. Food and Chemical Toxicology 2010; 48: 3289-3303
    CrossrefPubMedGoogle Scholar
  • 24 Ghanbarzadeh S, Garjani A, Ziaee M et al. CoQ10 and L-Carnitine Attenuate the Effect of High LDL and Oxidized LDL on Spermatogenesis in Male Rats. Drug Research 2014; In Press
    PubMedGoogle Scholar
  • 25 Delimaris I, Faviou E, Antonakos G et al. Oxidized LDL, serum oxidizability and serum lipid levels in patients with breast or ovarian cancer. Clinical Biochemistry 2007; 40: 1129-1134
    CrossrefPubMedGoogle Scholar
  • 26 Gorin A, Gabitova L, Astsaturov I. Regulation of cholesterol biosynthesis and cancer signaling. Current Opinion in Pharmacology 2012; 12: 710-716
    CrossrefPubMedGoogle Scholar
  • 27 Kummerow FA, Olinescu RM, Fleischer L et al. The relationship of oxidized lipids to coronary artery stenosis. Atherosclerosis 2000; 149: 181-190
    CrossrefPubMedGoogle Scholar
  • 28 Poirot M, Silvente-Poirot S. Cholesterol-5,6-epoxides: Chemistry, biochemistry, metabolic fate and cancer. Biochimie 2013; 95: 622-631
    CrossrefPubMedGoogle Scholar
  • 29 Poli G, Sottero B, Gargiulo S et al. Cholesterol oxidation products in the vascular remodeling due to atherosclerosis. Molecular Aspects of Medicine 2009; 30: 180-189
    CrossrefPubMedGoogle Scholar
  • 30 Yeh Y-H, Lee Y-T, Hsieh H-S et al. Effect of red yeast rice on toxicity of oxidized cholesterol and oxidized fish oil in rats. e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 2010; 5: e230-e237
    PubMedGoogle Scholar
  • 31 Duarte MMMF, Rocha JBT, Moresco RN et al. Association between ischemia-modified albumin, lipids and inflammation biomarkers in patients with hypercholesterolemia. Clinical Biochemistry 2009; 42: 666-671
    CrossrefPubMedGoogle Scholar
  • 32 Liu Y, Tang L, Chen B. Effects of antioxidant gene therapy on retinal neurons and oxidative stress in a model of retinal ischemia/reperfusion. Free Radical Biology and Medicine 2012; 52: 909-915
    CrossrefPubMedGoogle Scholar
  • 33 Rodriguez-Porcel M, Lerman A, Best PJM et al. Hypercholesterolemia impairs myocardial perfusion and permeability: role of oxidative stress and endogenous scavenging activity. Journal of the American College of Cardiology 2001; 37: 608-615
    CrossrefPubMedGoogle Scholar
  • 34 Soraya H, Farajnia S, Khani S et al. Short-term treatment with metformin suppresses toll like receptors (TLRs) activity in isoproterenol-induced myocardial infarction in rat: Are AMPK and TLRs connected?. International Immunopharmacology 2012; 14: 785-791
    CrossrefPubMedGoogle Scholar
  • 35 Ghanbarzadeh S, Garjani A, Ziaee M et al. Effects of L-Carnitine and Coenzyme Q10 on Impaired Spermatogenesis Caused by Isoproterenol in Male Rats. Drug Research 2014; In Press
    PubMedGoogle Scholar
  • 36 andalib S, Garjani A, Ghanbarzadeh S et al. Reduction of Coenzyme Q10 Content: A Possible Mechanism for Isoproterenol to Induce Heart Failure and Myocardial Infarction in Rat. Drug Research 2014; In Press
    PubMedGoogle Scholar
  • 37 I S, XM P, JH R. et al. The role of dietary oxidized cholesterol and oxidized fatty acids in the development of atherosclerosis. Mol Nutr Food Re 2005; 49: 1075-1082
    PubMedGoogle Scholar
  • 38 Baigent C, Clarke R. Cholesterol and Lipids. Journal 2008; pages
    PubMedGoogle Scholar
  • 39 Kullo IJ, Gau GT, Tajik AJ. Novel Risk Factors for Atherosclerosis. Mayo Clinic Proceedings 2000; 75: 369-380
    CrossrefPubMedGoogle Scholar
  • 40 Thompsen J, Thompson PD. A systematic review of LDL apheresis in the treatment of cardiovascular disease. Atherosclerosis 2006; 189: 31-38
    CrossrefPubMedGoogle Scholar
  • 41 Van Lente F. Markers of inflammation as predictors in cardiovascular disease. Clinica Chimica Acta 2000; 293: 31-52
    CrossrefPubMedGoogle Scholar
  • 42 Hasin Y, Shimoni Y, Stein O et al. Effect of cholesterol depletion on the electrical activity of rat heart myocytes in culture. Journal of Molecular and Cellular Cardiology 1980; 12: 675-683
    CrossrefPubMedGoogle Scholar
  • 43 Paila YD, Jindal E, Goswami SK et al. Cholesterol depletion enhances adrenergic signaling in cardiac myocytes. Biochimica et Biophysica Acta (BBA) – Biomembranes 2011; 1808: 461-465
    CrossrefPubMedGoogle Scholar
  • 44 Yaoita H, Yoshinari K, Maehara K et al. Different Effects of a High-Cholesterol Diet on Ischemic Cardiac Dysfunction and Remodeling Induced by Coronary Stenosis and Coronary Occlusion. Journal of the American College of Cardiology 2005; 45: 2078-2087
    CrossrefPubMedGoogle Scholar
  • 45 Ichihara S, Noda A, Yamada A et al. 1012-133 Statin therapy can improve cardiac function and survival after heart failure in rats. Journal of the American College of Cardiology 2004; 43: A160
    PubMedGoogle Scholar
  • 46 Miura S-i, Saku K. Effects of statin and lipoprotein metabolism in heart failure. Journal of Cardiology 2010; 55: 287-290
    CrossrefPubMedGoogle Scholar
  • 47 Xie R-q, Cui W, Liu F et al. Statin therapy shortens QTc, QTcd, and improves cardiac function in patients with chronic heart failure. International Journal of Cardiology 2010; 140: 255-257
    CrossrefPubMedGoogle Scholar
  • 48 Zhang S, Zhang L, Sun A et al. Efficacy of statin therapy in chronic systolic cardiac insufficiency: A meta-analysis. European Journal of Internal Medicine 2011; 22: 478-484
    CrossrefPubMedGoogle Scholar
  • 49 Mączewski M, Borys M, Kacprzak P et al. Late ventricular remodeling in non-reperfused acute myocardial infarction in humans is predicted by angiotensin II type 1 receptor density on blood platelets. International Journal of Cardiology 2008; 127: 57-63
    CrossrefPubMedGoogle Scholar
  • 50 Mączewski M, Mączewska J. Hypercholesterolemia Exacerbates Ventricular Remodeling in the Rat Model of Myocardial Infarction. Journal of Cardiac Failure 2006; 12: 399-405
    CrossrefPubMedGoogle Scholar
  • 51 Bastiaanse EML, Atsma DE, Kuijpers MMC et al. The Effect of Sarcolemmal Cholesterol Content on Intracellular Calcium Ion Concentration in Cultured Cardiomyocytes. Archives of Biochemistry and Biophysics 1994; 313: 58-63
    CrossrefPubMedGoogle Scholar
  • 52 Donck LV, Reempts JV, Vandeplassche G et al. A new method to study activated oxygen species induced damage in cardiomyocytes and protection by Ca2 + -Antagonists. Journal of Molecular and Cellular Cardiology 1988; 20: 811-823
    CrossrefPubMedGoogle Scholar
  • 53 Reboulleau A, Robert V, Vedie B et al. Involvement of cholesterol efflux pathway in the control of cardiomyocytes cholesterol homeostasis. Journal of Molecular and Cellular Cardiology 2012; 53: 196-205
    CrossrefPubMedGoogle Scholar
  • 54 D’Annunzio V, Donato M, Sabán M et al. Hypercholesterolemia attenuates postischemic ventricular dysfunction in the isolated rabbit heart. Molecular and Cellular Biochemistry 2005; 273: 137-143
    CrossrefPubMedGoogle Scholar
  • 55 Le Grand B, Vié B, Fauré P et al. Increased resistance to ischaemic injury in the isolated perfused atherosclerotic heart of the cholesterol-fed rabbit. Cardiovasc Res 1995; 30: 689-696
    CrossrefPubMedGoogle Scholar
  • 56 Van de Velde M, Dewolff M, Alex Leather H et al. Effects of lipids on the functional and metabolic recovery from global myocardial stunning in isolated rabbit hearts. Cardiovasc Res 2000; 48: 129-137
    PubMed
  • 57 Borchi E, Bargelli V, Stillitano F et al. Enhanced ROS production by NADPH oxidase is correlated to changes in antioxidant enzyme activity in human heart failure. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease 2010; 1802: 331–338.
    PubMedGoogle Scholar
  • 58 Limón-Pacheco J, Gonsebatt ME.. The role of antioxidants and antioxidant-related enzymes in protective responses to environmentally induced oxidative stress. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 2009; 674: 137-147
    CrossrefPubMedGoogle Scholar
  • 59 Morrissy S, Chen QM.. Oxidative Stress and Heart Failure. In: Charlene AM (ed). Comprehensive Toxicology, Oxford: Elsevier,. 2010: 221-242
    PubMedGoogle Scholar
  • 60 Singh M, Arya A, Kumar R et al. Dietary nitrite attenuates oxidative stress and activates antioxidant genes in rat heart during hypobaric hypoxia. Nitric Oxide 2012; 26: 61-73
    CrossrefPubMedGoogle Scholar
  • 61 Miyoshi T, Tian J, Matsumoto AH et al. Differential response of vascular smooth muscle cells to oxidized LDL in mouse strains with different atherosclerosis susceptibility. Atherosclerosis 2006; 189: 99-105
    CrossrefPubMedGoogle Scholar
  • 62 Nielsen LB. Atherogenecity of lipoprotein(a) and oxidized low density lipoprotein: insight from in vivo studies of arterial wall influx, degradation and efflux. Atherosclerosis 1999; 143: 229-243
    CrossrefPubMedGoogle Scholar
  • 63 Wang T-C, Hsu C-C, Chin Y-P et al. The autoantibody expression against different source of oxidized low density lipoprotein in patients with acute myocardial infarction. Thrombosis Research 2002; 107: 175-179
    CrossrefPubMedGoogle Scholar
  • 64 Anselmi M, Garbin U, Agostoni P et al. Plasma levels of oxidized-low-density lipoproteins are higher in patients with unstable angina and correlated with angiographic coronary complex plaques. Atherosclerosis 2006; 185: 114-120
    CrossrefPubMedGoogle Scholar
  • 65 Cominacini L, Anselmi M, Garbin U et al. Enhanced Plasma Levels of Oxidized Low-Density Lipoprotein Increase Circulating Nuclear Factor-Kappa B Activation in Patients With Unstable Angina. Journal of the American College of Cardiology 2005; 46: 799-806
    CrossrefPubMedGoogle Scholar
  • 66 Fernandes JL, Orford JL, Garcia C et al. Differences in human antioxidized LDL autoantibodies in patients with stable and unstable angina. Journal of Autoimmunity 2004; 23: 345-352
    CrossrefPubMedGoogle Scholar
  • 67 Vijayasarathy K, Shanthi Naidu K, Sastry BKS. Melatonin metabolite 6-Sulfatoxymelatonin, Cu/Zn superoxide dismutase, oxidized LDL and malondialdehyde in unstable angina. International Journal of Cardiology 2010; 144: 315-317
    CrossrefPubMedGoogle Scholar
  • 68 Siirtola A, Antikainen M, Ala-Houhala M et al. Studies of LDL particle size and susceptibility to oxidation and association with glucose metabolism in children after heart transplantation. The Journal of Heart and Lung Transplantation 2004; 23: 418-426
    CrossrefPubMedGoogle Scholar
  • 69 Bassi N, Ghirardello A, Iaccarino L et al. OxLDL/β2GPI-anti-oxLDL/β2GPI complex and atherosclerosis in SLE patients. Autoimmunity Reviews 2007; 7: 52-58
    CrossrefPubMedGoogle Scholar
  • 70 Min K-j, Um HJ, Cho K-H et al. Curcumin inhibits oxLDL-induced CD36 expression and foam cell formation through the inhibition of p38 MAPK phosphorylation. Food and Chemical Toxicology 2013; 58: 77-85
    CrossrefPubMedGoogle Scholar
  • 71 van Leeuwen M, Damoiseaux J, Duijvestijn A et al. The therapeutic potential of targeting B cells and anti-oxLDL antibodies in atherosclerosis. Autoimmunity Reviews 2009; 9: 53-57
    CrossrefPubMedGoogle Scholar
  • 72 Yin Y, Liu W, Ji G et al. The essential role of p38 MAPK in mediating the interplay of oxLDL and IL-10 in regulating endothelial cell apoptosis. European Journal of Cell Biology 2013; 92: 150-159
    CrossrefPubMedGoogle Scholar
  • 73 Patel V, Upaganlawar A, Zalawadia R et al. Cardioprotective effect of melatonin against isoproterenol induced myocardial infarction in rats: A biochemical, electrocardiographic and histoarchitectural evaluation. European Journal of Pharmacology 2010; 644: 160-168
    CrossrefPubMedGoogle Scholar
  • 74 Pinelli A, Trivulzio S, Tomasoni L et al. Isoproterenol-induced myocardial infarction in rabbits: Protection by propranolol or labetalol: a proposed non-invasive procedure. European Journal of Pharmaceutical Sciences 2004; 23: 277-285
    PubMedGoogle Scholar
  • 75 Rajadurai M, Stanely Mainzen Prince P. Preventive effect of naringin on cardiac markers, electrocardiographic patterns and lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats. Toxicology 2007; 230: 178-188
    CrossrefPubMedGoogle Scholar
  • 76 Upaganlawar A, Patel V, Balaraman R. Tomato lycopene attenuates myocardial infarction induced by isoproterenol: Electrocardiographic, biochemical and anti-apoptotic study. Asian Pacific Journal of Tropical Biomedicine 2012; 2: 345-351
    CrossrefPubMedGoogle Scholar
  • 77 Wang S-b, Tian S, Yang F et al. Cardioprotective effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. European Journal of Pharmacology 2009; 615: 125-132
    CrossrefPubMedGoogle Scholar
  • 78 Neefjes LA, ten Kate G-JR, Alexia R et al. Accelerated subclinical coronary atherosclerosis in patients with familial hypercholesterolemia. Atherosclerosis 2011; 219: 721-727
    CrossrefPubMedGoogle Scholar
  • 79 Shimizu M, Koizumi J, Miyamoto S et al. Electrocardiographic events and cholesterol reduction with pravastatin in patients with hypercholesterolemia: the Hokuriku Lipid Coronary Heart Disease Study-Pravastatin Atherosclerosis Trial. International Journal of Cardiology 2005; 99: 395-401
    CrossrefPubMedGoogle Scholar