Three Dangerous Loops Of Lipoproteine-Associated Phospholipase A2 Activity On Increasing LDL Aterogenecity
Background. Hypercholesterolemia is a major classic risk factor for cardiovascular disease, but there are 35%-40% cases of cardiovascular patients have a normal cholesterol levels. Lp-PLA2 is an enzyme that produced and secreted by macrophages as a response to the lipid peroxide formation, especially the platelet activating factor compound and phosphocholine peroxide. Lp-PLA2 is correlated with classic risk factor of cardiovascular disease, although that correlation with number of foam cell at early stage of atherosclerosis is not clear yet. This study aims to determine whether Lp-PLA2 levels correlated with classic risk factors of atherosclerosis and the number of foam cell, and the role of Lp-PLA2 enzyme in foam cells formation.Methods. This study observes the change of Lp-PLA2, F2-Isp, MDA, TC, LDL, HDL levels in rat serum at 3 levels of early atherogenesis, Ath-I, Ath-II and Ath-III were made on the number of foam cells. The number of cells was observed on all aortic cross sectional surfaces, using the Oil-Red-O staining. The LDL-C content was measure using the Fiedwall formula, MDA content was measure by using TBA-test, the observe of F2-isoprostane and Lp-PLA2 followed the procedure Elisa methods. Results. Anova test results among the 3 initial atherosclerotic levels showed a very significant difference (p<0.01) on Lp-PLA2 plasma content. The LSD test results represented an increase in Lp-PLA2 enzyme levels significantly since AthII stage. Path analysis refers that correlation value between the Lp-PLA2and the number of foam cell (r=0.48) were higher than that of the LDL (r=0.42), was neither correlated with MDA nor F2-Isp, the highest correlation occurred between Lp-PLA2 and LDL compared to the others parameters (r = 0.58). Path analysis also showed no correlation between cell numbers with MDA and F2-Isp, but LDL levels are correlated significantly with of oxidative stress markers MDA levels (r = 0.32) and correlated very significantly with F2-Isp (r = 0.69).Conclussion. It can be concluded that elevated levels of Lp-PLA2 increase atherogenecity of LDL, due to increased inflammation, stress oxidation and elevated levels of Lp-PLA2 itself, wich are interconnected with proatherogenic loops.
2.Stocker R and Keaney JF, 2005. Oxidative Stress and Atherosclerosis. In Localzo J. (ed) Molecular Mechanisms of Atherosclerosis. Taylor &Francis. London-New York pp. 82-114.
3.Shah PK, 2007. Molecular Mecha nisms of Palque Instability. Current Opinion in Lipidology 18: 492-499.
4.Ballantyne CM, O’Keee JH, Gotto AM, 2007. Dyslipidemia Essentials. Physician Press, New York. p. 1-63.
5.Howlett GJ and Moore KJ, 2006. Untangling the Role of Amyloid in Atherosclerosis. Current Opinion Lipidology 17: 541-547.
6.Ishigaki Y, Oka Y, Katagiri H, 2009. Circulating Oxidized LDL: a Biomarker And a Pathogenic Factor. Current Opinion in Lipidology 5: 363-369.
7.Anand DV, Lahiri A and Lipkin D, 2003. EBCT coronary calcium imaging for the early detection of coronary artery disease in asymptomatic individuals, J Cardiol 79: 10-17.
8.Miyamoto T, Yumoto H, Takakashi Y, Davey M, Gibson FC and Genco CA, 2006. Patogen accelerated Atherosclerosis Occur Early after Exposure and Can be Prevented via Immunization. Infection and Immunity 74: 1376-1380.
9.Ferri N, Paoletti R and Corsini A, 2006. Biomarker for Atherosclerosis: Pathophysiological Role and Pharmacological Modulation, Current Opinion in Lipidology17: 495-501.
10.Elstad MR, Stafforini DM, Prescott SM, McIntyre TM and Zimmerman, 1991. Human Macrophages Secrete Platelet-Activating Factor Acetylhydrolase. Chest 99 9S-10S.
11.Shi Y, Zhang P, Zhang L, Osman H, Mohler ER, Macphee C, Zalewski A, Postle A, Wilensky, 2007. Role of Lipoprotein-associated Phospholipase A2 in Leukocyte Activation and Inflammatory Responses. Atherosclerosis 191: 54-62.
12.Moriarty and Gibson, 2005. Effect of Low Density Lipoprotein Apheresis on Lipoprotein Associated Phospholipase A2. Am J Cardiol. 95: 1246-1247.
13.Noto H, Chitkara P and Raskin P, 2006. The Role of Lipoprotrein-Associated Phospholipase A2 in the Matabolic Syndrome and Diabetes. Journal of Diabetes ang the Complication. 20: 343-348.
14.Yang C, Chen H, Huang MT, Raya JL, Yang J, Chen C, Gaubatz JW, Pownall HJ, Taylor AA, Ballatyne CM, Jenniskens FA and Smith CV, 2007. Pro-apoptotic Low Density Lipoprotein Subfraction in TRype II Diabetes. Atherosclerosis. 193: 283-291.
15.Gorelick PB, 2008. Lipoprotein Assocoated phospholipase A2 and Risk of Stroke. Am. J. Cardiol. 101: 34F-40F.
16.Filippatos TD, Gazi IF, Liberopoulos VG, Elisaf MS, Tselepis AD and Kiortis DN, 2006. The Effect of Orsilat and Fenofibrate, alone or Combination, on Small dense LDL and Lipoprotein-associated Phospholipase A2 in Obese patients with Metabolic syndrome. Atherosclerosis. 193:428-437.
17.Persson M, Hedblad B, Nelson JJ, Berglund G, 2007. Elevated Lp-PLA2 Levels Add Prognostic Information to the Metabolic Syndrome on Incidence of Cardiovascular Events Among Middle-Aged Nondiabetic Subjects, Atheroscler Thromb Vasc Biol 10:1411=1416.
18.Mannheim D, Herrmann J, Versari D, Go¨ssl M, Meyer FB, McConnell JP, Lerman LO, Lerman A, 2008. Enhanced Expression of Lp-PLA2 and Lysophosphatidylcholine in Symptomatic Carotid Atherosclerotic Plaques, Stroke, 2008;39:1448-1455.
19.Silva IT., Mello AP., Damaceno RT. 2011. Antioxidant and inflammatory aspects of lipoprotein-associated phospholipase A2 (Lp-PLA2 ): A Review Lipids in Health and Disease, 10:170.
20.Gustone FD, 1996. Fatty Acid and Lipid Chemistry. Blackie Academic & Professional, New York. p. 81.
21.Iribarren C, 2006. Lipoprotein-Associated Phospholipase A2 and Cardiovascular Risk State of the evidence and Future Directions. Arteriosclerosis Thromb Vasc Biol. 26:5-6.
22.Wang Y and Oram JF, 2007. Unsaturated Fatty Acids phosphorylate and Destabilize ABCA1 Through a Protein Kinase C? Pathway. Journal of Lipid Research 48: 1062-1968.
23.Paramo JA, Rodriguez JA and Orbe J, 2006. Integrating Soluble Biomarkers and Imaging Technologies in The Identification of Vulnerable Atherosclerotic Patients. Biomarker Insight 1: 165-173.
24.Halliwell B, Guteridge JMC, 1999. Free Radicals in Biology and Medicine 3rd ed., Oxford University Press, NewYork. pp. 27-250.
25.Devaraj S, Hirany SV, Burk RF and Jialal I, 2001. Divergence between LDL Oxidative Susceptibility and Urinary F2-Isoprostanes as Measures of Oxidative Stress in Type 2 Diabetes. Clinical Chemistry 11: 1974-1979.
26.Reilly MP, Pratico D, Delanty N, DiMinno G, Tremoli E, Rader D, Kapoor S, Rokach J, Lawson J, FitzGerald G, 1998. Increased Formation of Distinct F2 Isoprostanes in Hypercholesterolemia, Circulation 98: 2822-2828.
27.Touyz RM and Schiffrin EL, 2007. Oxidative Stress and Hypertension. In Hotzman (ed) Atherosclerosis and Oxidant Atress : A New Perspective. Springer pp. 51-77.
28.Pezeshkian M, Nouri M, Zahraei M, Afrasiabi A and Abadi NA, 2001. Study of MDA, Antioxidant Vitamins, Lipoproteins Serum Levels and Anthropometry Parameters in Coronary Artery Disease Patients. Medical Journal of Islamic Academy of Sciences. 14: 5-8.
29.Kametsu Y, Kitagawa Y, Sekiyama S and Takagi S, 2005. Increase in Plasma Malondialdehyde-Modified Low-Density Lipoprotein in patients with Atherothrombotic Cerebral Infarction. Tokai J Exp Clin Med 30: 171-176.
30.Mogadam RAP, Nemati A and Baghi AN, 2008. Serum MDA as a Diagnostic’s Biomarker in Stable Coronary Heart Disease. Research Journal of Biological Sciences 3: 206-210.
31.Susilowati R, Sargowo D, Indra R, Tjokroprawiro A, Widyarti S, 2012. Korelasi antara Kadar Lp-PLA2, MDA, F2-Isp diserum dan Jaringan Aorta dengan jumlah sel busa dalam Proses aterogenesis pada Tikus Wistar, Jurnal Kardiologi Indonesia (33): 227-35.
32.Goncalves I, Wdsfeldt A, Young N K, Grufman H, Berg K, Bjorkbacka H, Nitulescu M, Persson A, Nilson M, Prehn C, Adamski J, Nilsson J, 2012. Lysophosphatidylcholine in Human Atherisclerotic Plaque Inflammation, Atheroscler Thromb Vasc Biol.: 1505-1512.
33.Stafforini D, Sheller JR, Blackwell TS, Sapirstein A, Yull FE, Mcientyre TM, Bonventre JV, Prescott SM and Roberts LJ, 2005. Release of F2-isoprostanes from Esterified Phospholipids Is Catalyzed by Intracellular and Plasma Platelet-activating Factor Acetylhydrolases. The Journal og Biological and Chemistry. 28: 4616-4623.
34.Karabina SA, Brocheriou I, Naour GL, Agrapart M, Durand H, Gelb M, Lambeau G and Ninio E, 2006. Atherogenic Properties of LDL Particles Modified by Human Group X Secreted Phospholipase A2 on Human Endothelial Cell Function, The Faseb Journal 20: E1890-E1900.
35.Liao W, Liu C and Wang C, 2008. Detection of lipoprotein-associated phospholipase A2 using a nano-iridium particle catalyst-based biosensor, SensorsandActuators B (134): 993-999.
36.Feistein SB, 2008. Vascular Imaging. Feinstein (ed). Non Invasive Surrogate Marker of Atherosclerosis, Informa Healthcare, Informa KU Ltd, London pp. 85-87.
37.Zalewski A and Macphee C, 2005. Role of Lipoprotein-Associated Phospholipase A2 in Atherosclerosis: Biology, Epidemiology, and Posible Thearpeutic Target, Journal of The American Heart Assocoation 25: 923-931.
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