Role of homocysteine and lipoprotein (A) in atherosclerosis: An update

Biomedical Research

Volumn 22, Issue 4, 2011, Pages 391-405

  Tayal, Devika ^a   Goswami, Binita ^b   Koner, Bidhan Chandra ^c   Mallika, V ^b  

^a LADY HARDINGE MEDICAL COLLEGE   (India)

^b G B PANT HOSPITAL   (India)

^c MAULANA AZAD MEDICAL COLLEGE   (India)

Author keywords

Atherosclerosis; Atherothrombosis; CAD; Coronary artery disease; Homocysteine; Lipoprotein (a)

Indexed keywords

HOMOCYSTEINE; LIPOPROTEIN A;

ATHEROGENESIS; ATHEROSCLEROSIS; BINDING AFFINITY; CORONARY ARTERY DISEASE; DISEASE ASSOCIATION; DNA METHYLATION; HUMAN; MOLECULAR PATHOLOGY; NONHUMAN; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REVIEW; RISK FACTOR; THROMBOCYTE FUNCTION;

EID: 80053984729     PISSN: 0970938X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (155)

1. Fleming R M. Angina and coronary ischemia are the results of coronary regional blood flow differences. J Amer Coll Angiol 2003; 1:127-142.
2. Mallika V, Goswami B, Medha R. Atherosclerosis pathophysiology and role of novel risk factors: A clini-cobiochemical Perspective. Angiology. 2007; 58(5):513-522.
3. Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 1997; 349:1269-1276.
4. Mohan V, Deepa R, Rani SS, Premlatha G. Prevalence of coronary artery disease and its relationship to lipids in a selected population in south India: CUPS No 5. J. Am Coll Cardiol. 2001; 38:682-687.
5. Libby P. Inflammation in atherosclerosis. Nature 2002; 420: 868-874.
6. Berg, K. 1963. A new serum type system, the lp system. Acta Pathol. Microbiol. Scand.; 59: 369-382.
7. G. Lippi and Guidi G. Lipoprotein (a): from ancestral benefit to modern pathogen? Q J M 2000; 93: 75-84.
8. Berg K. Lp(a) lipoprotein: an overview. Chem Phys Lipids 1994; 67-68:9-16.
9. Guevara J Jr, Valentinova NV, Garcia O, Gotto AM, Yang CY, Legal S, Gaubatz J, Sparrow JT. Interaction of apolipoprotein[a] with apolipoproteinB-100 Cys3734 region in lipoprotein[a] is confirmed immu-nochemically. J Protein Chem 1996; 15:17-25.
10. Callow MJ, Rubin EM. Site-specific mutagenesis demonstrates that cysteine 4326 of apolipoprotein B is required for covalent linkage with apolipoprotein (a) in vivo. J Biol Chem 1995; 270: 23914-23917.
11. Magnaghi P, Citterio E, Malgaretti N, Acquati F, Otto-lenghi S, Taramelli R. Molecular characterisation of the human apo(a)-plasminogen gene family clustered on the telomeric region of chromosome 6 (6q26-27). Hum Mol Genet 1994; 3:437-42.
12. Yamamura Y, Yamashiro K, Tsuruoka N, Nakazato H, Tsujimura A, Yamaguchi N. Molecular cloning of a novel brain-specific serine protease with a kringle-like structure and three scavenger receptor cysteine-rich motifs. Biochem Biophys Res Commun.1997; 239: 386-92.
13. Byrne CD, Schwartz K, Meer K, Cheng JF, Lawn RM. The human apolipoprotein (a) /plasminogen gene cluster contains a novel homologue transcribed in liver. Ar-terioscler Thromb.1994; 14: 534-41.
14. Mbewu AD and Durrington PN. Lipoprotein (a): structure and possible involvement in thrombogenesis and atherogenesis. Atherosclerosis 1990; 85: 1-14.
15. Kraft HG, Lingenhel A, Kochl S, et al. Apolipoprotein (a) kringle IV repeat number predicts risk for coronary heart disease. Arterioscler Thromb Vasc Biol 1996; 16: 713-719.
16. Hobbs HH, White AL. Lipoprotein (a): Intrigues and insights. Curr Opin Lipidol.1999; 10: 225-236.
17. Berglund L. Diet and drug therapy for lipoprotein (a). Curr Opin Lipidol 1995; 6: 48-56.
18. Geethanjali FS, Luthra K, Lingenhel A, Kanagasaba-Pathy AS, Jacob J, Srivastava LM, Vasisht S, Kraft HG, Utermann G. Analysis of the apo(a) size polymorphism in Asian Indian populations: association with Lp(a) concentration and coronary heart disease. Atherosclerosis 2003; 169: 121-130
19. Hughes K, Aw TC, Kuperan P, Choo M. Central obesity, insulin resistance, syndrome X, lipoprotein (a) and cardiovascular risk in Indians, Malays, and Chinese in Singapore. J Epidemiol Community Health 1997; 51: 394-399.
20. Hoogeveen RC, Gambhir JK, Gambhir DS, Kimball KT, Ghazzaly K, Gaubatz JW, Vaduganathan M, Rao RS, Koschinsky M, Morrisett JD. Evaluation of Lp(a) and other independent risk factors for CHD in Asian Indians and their USA counterparts. J Lipid Res. 2001; 42: 631-638
21. Utermann G. Genetic architecture and evolution of the lipoprotein (a) trait. Curr Opin Lipidol 1999; 10: 133-141.
22. Kraft HG, Lingenhel A, Pang RWC, Delport R, Trommsdorf M, Vermaak H, Janus ED, Utermann G. Frequency distributions of apolipoprotein (a) kringle IV repeat alleles and their effects on lipoprotein (a) levels in Caucasian, Asian, and African populations: the distribution of null alleles is non-random. Eur J Hum Genet 1996; 4: 74-87.
23. Lars BL and Ramakrishnan R. Lipoprotein (a): An Elusive Cardiovascular Risk Factor. Arteriosclerosis, Thrombosis, and Vascular Biology 2004;24:2219-2226.
24. Trommsdorff M, Köchl S, Lingenhel A, Kronenberg F, Delport R, Vermaak H, Lemming L, Klausen C, Faergeman O, Utermann G, Kraft H-G. A pentanucleo-tide repeat polymorphism in the 5' control region of the apolipoprotein (a) gene is associated with lipoprotein (a) plasma concentrations in Caucasians. J Clin In-vest.1995; 96: 150-157.
25. Mooser V, Mancini FP, Bopp S, Pethö-Schramm A, Guerra R, Boerwinkle E, Müller H-J, Hobbs HH. Sequence polymorphisms in the apo(a) gene associated Biomedical Research 2011 Volume 22 Issue 4 with specific levels of Lp(a) in plasma. Hum Mol Genet 1995; 4: 173-181.
26. Rubin J, Pearson TA, Reed RG, Berglund L. A fluorescence-based, non-radioactive method for efficient detection of the pentanucleotide repeats (TTTTA) n polymorphism in the apolipoprotein (a) gene. Clin Chem.2001; 47: 1758-1762.
27. Rodriguez CR, Seman LJ, Ordovas JM, Jenner J, Genest MS Jr, Wilson PW, Schaefer EJ. Lipoprotein (a) and coronary heart disease. Chem Phys Lipids 1994; 67-68:389-98.
28. Lippi G, Guidi G. Biochemical risk factors and patient's outcome: the case of lipoprotein (a). Clin Chim Acta. 1999; 280:59-71.
29. Pillarisetti S, Paka L, Obunike JC, Berglund L, Goldberg IJ. Subendothelial retention of lipoprotein (a): evidence that reduced heparan sulfate promotes lipopro-tein binding to subendothelial matrix. J Clin In-vest.1997; 100:867-874.
30. Grainger DJ, Kemp PR, Liu AC, Lawn RM, Metcalfe JC. Activation of transforming growth factor-beta is inhibited in transgenic apolipoprotein (a) mice. Nature 1994; 370:460-462.
31. Poon M, Zhang X, Dunsky KG, Taubman MB, Harpel PC. Apolipoprotein (a) induces monocyte chemotactic activity in human vascular endothelial cells. Circulation 1997; 96:2514-2519.
32. Naruszewicz M, Selinger E, Davignon J. Oxidative modification of lipoprotein (a) and the effect of ß-carotene. Metabolism 1992; 41:1215-24.
33. Loscalzo J. Lipoprotein (a): a unique risk factor for atherothrombotic disease. Arteriosclerosis 1990; 10: 672-679.
34. Li XN, Grenett HE, Benza RL, et al. Genotype-specific transcriptional regulation of PAI-1 expression by hy-pertriglyceridemic VLDL and Lp(a) in cultured human endothelial cells. Arterioscler Thromb Vasc Biol.1997; 17:3215-3223.
35. Levin EG, Miles LA, Fless GM, et al. Lipoproteins inhibit the secretion of tissue plasminogen activator from human endothelial cells. Arterioscler Thromb.1994; 14: 438-442.
36. Riis HP, Kharazmi A, Jauhianen M, Ehnholm C. Induction of oxygen free radical generation in human monocytes by lipoprotein (a). Eur J Clin Invest.1994; 24:497-9.
37. Edelstein C, Pfaffinger D, Hinman J, Miller E, Lipkind G, Tsimikas S, Bergmark C, Getz GS, Witztum JL, Scanu AM. Lysine-phosphatidylcholine adducts in kringle V impart unique immunological and potential pro-inflammatory properties to human apolipoprotein (a). J Biol Chem.2003; 278: 52841-52847.
38. Silaste ML, Rantala M, Alfthan G, Aro A, Witztum JL, Kesäniemi YA, Hörkkö S. Changes in dietary fat intake alter plasma levels of oxidized low-density lipoprotein and lipoprotein (a). Arterioscler Thromb Vasc Biol 2004; 24: 498-503.
39. Tsimikas S, Bergmark C, Beyer RW, Patel R, Pattison J, Miller E, Juliano J, Witztum JL. Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes. J Am Coll Cardiol 2003; 41: 360-370.
40. Edelstein C, Pfaffinger D, Hinman J, et al. Lysine-phosphatidylcholine adducts in Kringle V impart unique immunological and potential pro-inflammatory properties to human apolipoprotein (a). J Biol Chem 2003; 278: 52841-52847.
41. Takami S, Yamashita S, Kihara S, Ishigami M, Take-mura K, Kume N, Kita T, and Matsuzawa Y. Lipopro-tein (a) enhances the expression of intercellular adhesion molecule-1 in cultured human umbilical vein en-dothelial cells. Circulation 1998; 97: 721-728.
42. Allen S, Khan S, Tam S, Koschinsky M, Taylor P, and Yacoub M. Expression of adhesion molecules by Lp(a): a potential novel mechanism for its atherogenicity. FASEB J.1998;12:1765-1776.
43. Berge K E, Djurovic S, Muller H J, Alestrom P, and Berg K. Studies on effects of Lp(a) lipoprotein on gene expression in endothelial cells in vitro).Clin. Genet 1997; 52: 314-325.
44. Haque N S, Zhang X, French D L, Li J, Poon M, Fallon JT, Gabel BR, Taubman, MB, Koschinsky M, and Har-pel P. 2000. Chemokine I-309 Is the Principal Mono-cyte Chemoattractant Induced by Apolipoprotein (a) in Human Vascular Endothelial Cells. Circulation 2000; 102:786-792.
45. Grainge, DL, Kemp PR, Liu AC, Lawn RM, and Met-calfe JC. Activation of transforming growth factor-β is inhibited in transgenic apolipoprotein (a) mice. Nature 1994; 370:460-462.
46. Luc G, Bard JM, Arveiler D, et al. Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study. Atherosclerosis 2002; 163: 377-384
47. Bostom AG, Gagnon DR, Cupples LA, Wilson PW, Jenner JL, Ordovas JM, et al. A prospective investigation of elevated lipoprotein (a) detected by electropho-resis and cardiovascular disease in women. The Fram-ingham Heart Study Circulation 1994; 90:1688-95.
48. Schaefer EJ, Lamon-Fava S, Jenner JL, McNamara JR, Ordovas JM, Davis CE, et al. Lipoprotein (a) levels and risk of coronary heart disease in men. The Lipid Research Clinics Coronary Primary Prevention Trial. JAMA 1994; 271:999-1003.
49. Rosengren A, Wilhelmsen L, Eriksson E, Risberg B, Wedel H. Lipoprotein (a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men. BMJ 1990; 301:1248-51.
50. Genest J Jr, Jenner JL, McNamara JR, Ordovas JM, Silverman SR, Wilson PW, et al. Prevalence of lipopro-tein (a) [Lp(a)] excess in coronary artery disease. Am J Cardiol 1991; 67:1039-1045.
51. Budde T, Fechtrup C, Bosenberg E, Vielhauer C, Enbergs A, Schulte H, et al. Plasma Lp(a) levels correlate with number, severity, and length-extension of coronary lesions in male patients undergoing coronary arteriography for clinically suspected coronary atherosclerosis. Arterioscler Thromb.1994; 14:1730-6.
52. Dahlen GH, Guyton JR, Attar M, Farmer JA, Kautz JA, Gotto AM Jr. Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation 1986; 74:758-65.
53. Bostom AG, Cupples LA, Jenner JL, Ordovas JM, Se-man LJ, Wilson PW, et al. Elevated plasma lipoprotein (a) and coronary heart disease in men aged 55 years and younger. A prospective study. JAMA 1996; 276:544-8.
54. Sandkamp M, Funke H, Schulte H, Kohler E, Assmann G. Lipoprotein (a) is an independent risk factor for myocardial infarction at a young age. Clin Chem 1990; 36:20-3.
55. Durrington PN, Ishola M, Hunt L, Arrol S, Bhatnagar D. Apolipoproteins(a), AI, and B and parental history in men with early onset ischaemic heart disease. Lancet 1988; 1(8594):1070-3.
56. Genest J Jr, McNamara JR, Ordovas JM, Jenner JL, Silberman SR, Anderson KM, et al. Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease. J Am Coll Cardiol.1992; 19:792-802.
57. Cremer P, Nagel D, Labrot B, Mann H, Muche R, Elster H, et al. Lipoprotein Lp(a) as predictor of myo-cardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Gottingen Risk Incidence and Prevalence Study (GRIPS). Eur J Clin Invest. 1994; 24:444-53.
58. Rhoads GG, Dahlen G, Berg K, Morton NE, Dannenberg AL. Lp(a) lipoprotein as a risk factor for myocardial infarction. JAMA.1986; 256:2540-4.
59. Desmarais RL, Sarembock IJ, Ayers CR, Vernon SM, Powers ER, Gimple LW. Elevated serum lipoprotein (a) is a risk factor for clinical recurrence after coronary balloon angioplasty. Circulation 1995; 91:1403-9.
60. Zenker G, Koltringer P, Bone G, Niedorkorn K, Pfeif-fer K, Jurgen G. Lipoprotein (a) as a strong indicator for cerebrovascular disease. Stroke 1989; 17:942-5.
61. Chambless LE, Shahar E, Sharrett AR, Heiss G, Wijnberg L, Paton CC, et al. Association of transient ischemic attack/stroke symptoms assessed by standardized questionnaire and algorithm with cerebrovascular risk factors and carotid artery wall thickness. The ARIC Study, 1987-1989. Am J Epidemiol. 1996; 144:857-66.
62. Van Kooten F, van Krimpen J, Dippel DW, Hooger-brugge N, Koudstaal PJ. Lipoprotein (a) in patients with acute cerebral ischemia. Stroke 1996; 27:1231-5.
63. Solymoss BC, Marcil M, Wesolowska E, Lesperance J, Pelletier LC, Campeau L. Risk factors of venous aorto-coronary bypass graft disease noted at late symptom-directed angiographic study. Can J Cardiol.1993; 9:80-4.
64. Barbir M, Kushwaha S, Hart B, Macken H, Thompson GR, Mitchell A, et al. Lipoprotein (a) and accelerated coronary artery disease in cardiac transplant recipients. Lancet 1992; 340:1500-2.
65. Orth-Gomer K, Mittleman MA, Schenk-Gustafsson K, Wamala SP, Eriksson M, Belkic K, et al. Lipoprotein (a) as a determinant of coronary heart disease in young women Circulation 1997; 95: 329-334.
66. Schreiner PJ, Heiss G, Tyroler HA, Morrisett JD, Davis CE, Smith R. Race and gender differences in the association of Lp(a) with carotid artery wall thickness. The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vasc Biol.1996; 16: 471-478.
67. Schreiner PJ, Chambless LE, Brown SA, Watson RL, Toole J, Heiss G. Lipoprotein (a) as a correlate of stroke and transient ischemic attack prevalence in a bi-racial cohort: the ARIC Study. Atherosclerosis Risk in Communities. Ann Epidemiol.1994; 4:351-9.
68. Dhawan J. Coronary heart disease risks in Asian Indians. Curr Opin Lipidol. 1996; 7:196-8.
69. Sunayama S, Daida H, Mokuno H, Miyano H, Yokoi H, Lee YJ, et al. Lack of increased coronary atherosclerotic risk due to elevated lipoprotein (a) in women > or = 55 years of age. Circulation 1996; 94:1263-8.
70. Ridker PM, Hennekens CH, Stampfer MJ. A prospective study of lipoprotein (a) and the risk of myocardial infarction. JAMA 1993; 270:2195-9.
71. Ridker PM, Stampfer MJ, Hennekens CH. Plasma concentration of lipoprotein (a) and the risk of future stroke. JAMA.1995; 273:1269-73.
72. Jauhiainen M, Koskinen P, Ehnholm C, Frick MH, Manttari M, Manninen V, et al. Lipoprotein (a) and coronary heart disease risk: a nested case-control study of the Helsinki Heart Study participants. Atherosclerosis 1991; 89:59-67.
73. Cantin B, Gagnon F, Moorjani S, Despres JP, La-marche B, Lupien PJ, et al. Is lipoprotein (a) an independent risk factor for ischemic heart disease in men? The Quebec Cardiovascular Study. J Am Coll Cardiol 1998; 31:519-25.
74. Moliterno DJ, Jokinen EV, Miserez AR, Lange RA, Willard JE, Boerwinkle E, et al. No association between plasma lipoprotein (a) concentrations and the presence or absence of coronary atherosclerosis in African-Americans. Arterioscler Thromb Vasc Biol 1995; 15:850-5.
75. Sharobeem KM, Patel JV, Ritch AE, Lip GY, Gill PS, Hughes EA. Elevated lipoprotein (a) and apolipopro-tein B to AI ratio in South Asian patients with ischae-mic stroke. Int J Clin Pract. 2007; 61(11):1824-8.
76. Rajappa M, Sridhar MG, Balachander J, Sethuraman KR. Lipoprotein (a) and comprehensive lipid tetrad index as a marker for coronary artery disease in NIDDM patients in South India. Clin Chim Acta. 2006; 372(1-2):70-5.
77. Goswami B, Rajappa M, Mallika V, Singh B, Ray PC, Kumar S. Inflammation and Dyslipidemia: a possible interplay between established risk factors in north Indian males with coronary artery disease. Cardiovascular Journal of South Africa 2010; 21(2): 107-12.
78. Singh S, Dwivedi S, Melkani GC, Rani C, Gaur SP, Mandal SK, Mahua J. Lipoprotein(a) and coronary heart disease in Indian population. JAPI 1999; 47(12): 1157-60.
79. Gambhir JK, Harsimrut K, Gambhir DS and Prabhu KM. Lipoprotein (a) as an independent risk factor for Coronary artery disease in patients below 40 years of age. IHJ.2000; 52: 411-415.
80. Enas EA and Senthilkumar A. Role of Lipoprotien(a): Reality and Relevance. In: Gambhir, D. (ed.) Cardiology Update 2000. CSI, New Delhi p 8-25.
81. Gambhi, JK, Gambhir DS and Morreset J. Lipoprotein (a) in normal Indian subjects and patients with coronary artery disease. IHJ. 1998; 50: 563.
82. Gupta R, Kastia S, Rastogi S, Kaul V, Nagar R and Enas EA. Lipoprotein(a) in Coronary Heart Disease: A Case-Control Study. IHJ.2002; 52: 407- 410.
83. Mohan V, Deepa R and Rema M. Lipoprotein (a) and coronary artery disease in Indians. JAPI 1998; 46, 979-980.
84. McCully KS. Vascular pathology of homocysteinemia. Implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56:111-128
85. Coltaneo M. Hyperhomocysteinemia. Atherosclerosis and Thrombosis. Thromb Haemost.1999; 81:165-76.
86. Haynes WG. Hyperhomocysteinemia V, vascular function and atherosclerosis: effect of vitamins. Cardiovascular Drugs and Therapy 2002; 16:391-399.
87. Rasmussen K, Moller J. Total homocysteine measurement in clinical practice. Ann Clin Biochem.2000; 37: 627-648.
88. Finkelstein JD. Methionine metabolism in mammals. J Nutri Biochem.1990;1: 228-37.
89. Wilcken DEL, Wilcken B. The pathogenesis of coronary artery disease. A possible role for methionine metabolism. J Clin Invest 1976; 57: 1079-82.
90. Ziegler DM. Role of reversible oxidation-reduction of enzyme thiols-disulfides in metabolic regulation. Annu Rev Biochem.1985; 54: 305-29.
91. Esmon CT, Owen WG. Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc Natl Acad Sci USA 1981; 78: 2249-52.
92. Rodgers GM. Hemostatic properties of normal and perturbed vascular cells. FASEB J 1988; 2: 116-23.
93. Hajjar K. Assembly of the fibrinolytic system on endo-thelial cells. In: Haber E, Braunwald E, eds. Throm-bolysis: Basic Contributions and Clinical Progress. Mosby-Year Book 1991: 27-32.
94. Hajjar KA. Homocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor. J Clin Invest 1993; 91: 2873-9.
95. Rodgers GM, Kane WH. Activation of endogenous factor V by a homocysteine-induced vascular endothe-lial cell activator. J Clin Invest 1986; 77: 1909-16.
96. Lentz SR, Sadler JE. Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic agent homocysteine. J Clin Invest 1991; 88:1906-1914.
97. Nishinaga M, Ozawa T, Shimado K. Homocysteine, a thrombogenic agent, suppresses anticoagulant heparin suphate expression in cultured procine aortic endothe-lial cells. J Clin Invest 1993; 92: 1381-1386.
98. Broekman MJ, Haijar KA, Marcus AJ, Lev E, Islam N, Safier LB, Flreosbach J. Homocysteine inhibits ecto ADPase activity of human umbilical vein endothelial cells. Blood 1994; 84 (Suppl):77-80.
99. Ross R. The pathogenesis of atherosclerosis-an update. N Engl J Med 1986; 314: 488-500.
100. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362 (6423): 801-9.
101. Dudman NP, Temple SE, Guo XW, Fu W, Perry MA. Homocysteine enhances neutrophil-endothelial interactions in both cultured human cells and rats in vivo. Circ Res 1999;84:409-16.
102. Poddar R, Sivasubramaniam N, Robinson K, Jacobsen DW. Homocysteine modulates the expression of a specific cytokine (Monocyte chemoattractant protein-1) in human aortic endothelial cells. Circulation 1997; 96: I-286.
103. Harker LA, Ross R, Slichter SJ, Scolt CR. Homo-cystine - induced arterosclerosis: the role of endothelial cell injury and platelet response in its genesis. J Clin Invest.1996; 58: 731-41.
104. Wall RT, Harlan JM, Harker LA, Striker GE. Homo-cysteine induced endothelial cell injury in vivo: A review. Thromb Res.1980; 18:113-121.
105. Wang H, Yoshizumi M, Lai K. Inhibition of growth and p21ras methylation in vascular endothelial cells by homocysteine but not cysteine. J Biol Chem 1997; 272: 25380-25385.
106. Dudman NPB, Temple SE, Guo XW, Fu WY, Perry MA. Homocysteine enhances neutrophil endothelial interactions in vivo. Circ Res 1999; 84: 409-416.
107. Haynes WG. Hyperhomocysteinemia Vascular function and atherosclerosis: Effect of vitamins. Cardiovascular Drugs and therapy 2002; 16:391-99.
108. Starkebaum G, Harlan JM. Endothelial cell injury due to copper catalysed hydrogen peroxide generation from homocysteine. J Clin Invest 1993; 77:1370-1376.
109. Heinecke JW, Rosen H, Suzuki LA, Chait A. The role of sulphur containing amino acids in superoxide production and modification of low density lipoprotein in arterial smooth muscle cells. J Biol Chem 1987; 262: 10098-10103.
110. Upchurch GR, Welch GN, Fabian AJ. Homocysteine decreases bioavailable Nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem 1997; 272: 17012-17017.
111. Emsley AM, Jeremy JV, Gomes GN, Angelini GD, Plane F. Investigation of the inhibitory effects of ho-mocysteine and copper on nitric oxide mediated relaxation of rat isolated aorta. Brit J Pharmacol.1999; 126: 1034-1040.
112. Rolland PH, Friggi A, Barlatier A, Piquet P, Latrille V, Faye MM. Hyperhomocysteinemia induced vascular damage in pig circulation. Circulation 1995; 91: 1161-1174.
113. Liao D, Tan H, Hui R, Li Z, Jiang X, Gaubatz J, Yang F, Durante W et al,. Hyperhomocysteinemia Decreases Circulating High-Density Lipoprotein by Inhibiting Apolipoprotein A-I Protein Synthesis and Enhancing HDL Cholesterol Clearance. Circulation Res. 2006; 99:598-603.
114. Boger RH. The emergent role of asymmetric dimethy-largine as a novel cardiovascular risk factor. Cardio Vasc Res 2003; 59: 824-833.
115. Hiltunen MO, Via-Herttual S. 2000. DNA methylation smooth muscle cells and atherogenesis. Arterioscler Thromb Vasc Biol; 20: 1557-1564.
116. Fryer RH, Wilson BD, Gubler DB, Fitzgerald LA, Rodgers GM. Homocysteine, a risk factor for premature vascular disease and thrombosis, induces tissue factor activity in endothelial cells. Arterioscler & Thrombosis 1993; 13: 1327-33.
117. Krumkan II, Culmsee C, Chan SL, Kruman Y, Guo Z, Penix L, Matson MR. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to cxcitotoxicity. J Neurosci 2000; 20(18): 6920-6926.
118. Bostom AG, Silbershatz H, Rosenberg IH, et al. Non-fasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Fram-ingham men and women. Arch Intern Med.1999; 159: 1077-1080.
119. Folsom AR, Nieto FJ, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation 1998; 98: 204-210.
120. Perry IJ, Refsum H, Morris RW, et al. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 1995; 346: 1395-1398.
121. Nurk E, Tell GS, Vollset SE, et al. Plasma total homo-cysteine and hospitalizations for cardiovascular disease: the Hordaland Homocysteine Study. Arch Intern Med.2002; 162: 1374-1381.
122. Boushey CJ, Beresford SAA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995; 274: 1049-57.
123. Stampfer MJ, Malinow MR, Willett WC, Newcomer LM, Upson D, Tiswer PV, Hennekens CH. A prospective study of plasma homocysteine and risk of myocardial infarction in US physicians. JAMA 1992; 268: 877-81.
124. Montalescot G, Ankri A, Chadefau X, Vekemans B. Plasma homocysteine and the extent of atherosclerosis in patients with coronary artery disease. Int J Cardiol 1997; 60:295-300.
125. Nygard O, Nordvehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Eng J Med 1997; 337: 230-236.
126. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG. MTHFR Studies Collaboration Group MTHFR 677C T polymorphism and risk of coronary heart diseases meta-analysis. JAMA 2002; 288:2023-2031.
127. Antoniades C, Antonopoulos A.S, Tousoulis D, Marinou Kand Stefanadis C. Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials. European Heart Journal 2009; 30 (1):6-15.
128. Kaul S, Zadeh AA and Prediman K. Shah PK. Homo-cysteine Hypothesis for Atherothrombotic Cardiovascular Disease.Not Validated. Am Coll Cardiol 2006; 48:914-923.
129. McCully KS. Homocysteine, folate, vitamin B6 and cardiovascular disease. JAMA 1998; 279:392-3.
130. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence of causality from a meta-analysis. Br Med J 2002; 325: 1202-1209.
131. Humphrey LL, Fu R, Rogers K, Freeman M, Helfand M. Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo Clin Proc.2008; 83(11):1200-2.
132. Cleophas TJ, et al. Homocysteine, a risk factor for coronary artery disease or not? A meta-analysis. J Am Coll Cardiol 2000; 86:1005-9.
133. Brilakis ES, McConnell JP, Ballman KV, Klee GG, Berger PB. Lack of association between plasma homo-cysteine and angiographic coronary artery disease in the era of fortification of cereal grain flour with folic acid. Atherosclerosis 2002; 165(2):375-81.
134. Lakshmi AV, Maniprabha C and Krishna TP. Plasma homocysteine level in relation to folate and vitamin B6 status in apparently normal men. Asia Pacific J Clin Nutr 2001; 10(3): 194-196.
135. Puri A, Gupta OK, Dwivedi RN, Bharadwaj RP, Na-rain VS, Singh S. Homocysteine and lipid levels in young patients with coronary artery disease. JAPI 2003; 51:681-5.
136. Bhargava S, Parakh R and Srivastava LM. Studies on homocysteine demonstrating its significance as a possible tool for differential diagnosis in occlusive vascular disease. IJCB 2004; 19(1):76-78.
137. Abraham R, John MJ, Dhanoa CJ. Raised serum homo-cysteine levels in patients of coronary artery disease and the effect of vitamin B12 and folate on its concentration. IJCB 2006; 21 (1): 95-100.
138. Rao H, Govindaraju V, Manjunath CN. Risk prediction - homocysteine in coronary heart disease. IJCB 2007; 22 (1):18-21.
139. Pandey SN, Vaidya AD, Vaidya RA, Talwalkar S. Hy-perhomocysteinemia as a cardiovascular risk factor in Indian women: determinants and directionality. JAPI 2006; 54: 769-774.
140. Deepa R, Velmurugan K, Saravanan G, Karkuzhali K, Dwarakanath V, Mohan V. Absence of Association between Serum Homocysteine Levels and Coronary Artery Disease in South Indian Males. IHJ 2001; 53: 44- 47.
141. Maher VM, Brown BG, Marcovina SM, Hillger LA, Zhao XQ, Albers JJ. Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein (a). JAMA.1995; 274: 1771-1774
142. Cantin B, Gagnon F, Moorjani S, Despres JP, La-marche B, Lupien PJ, Dagenais GR. Is lipoprotein (a) an independent risk factor for ischemic heart disease in men? The Quebec Cardiovascular Study. J Am Coll Cardiol.1998; 31: 519-525
143. Von Eckardstein A, Schulte H, Cullen P, Assman G. Lipoprotein (a) further increases the risk of coronary events in men with high global cardiovascular risk. J Am Coll Cardiol. 2000; 201; 37: 434-439.
144. Harpel PC, Chang VT, Wolfgangborth E. Homocys-teine and other sulfhydryl compounds enhance the binding of lipoprotein (a) to fibrin: A potential biochemical link between thrombosis, atherogenesis, and sulflhydryl compound metabolism. Proc. NatL. Acad. Sci. 1992; 89:10193-10197.
145. Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B & Graham I. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 1991; 324: 1149-1155.
146. Foody JM, Milberg JA, Robinson K, Pearce GL, Jacobsen DW, Sprecher DL. Homocysteine and Lipo-protein (a) Interact to Increase CAD Risk in Young Men and Women. Arterioscl Thromb Vasc Biol.2000; 20: 493-98.
147. Lawn RM, Wade DP, Hammer RE, Chiesa G, Verstuyft JG, Rubin EM. Atherogenesis in transgenic mice expressing human apolipoprotein (a). Nature 1992; 360: 670-672.
148. Ghorbanihaghjo A, Javadzadeh A, Argani H, Nezami N, Rashtchizadeh N, Rafeey M, Rohbaninoubar M,2 and Rahimi-Ardabili B. Lipoprotein(a), homocysteine, and retinal arteriosclerosis. Mol Vis 2008; 14: 1692-1697.
149. Nardulli M, Durlach V, Pepe G, Anglés-Cano E. Mechanism for the homocysteine-enhanced antifibri-nolytic potential of lipoprotein (a) in human plasma. Thromb Haemost. 2005; 94 (1): 75-81.
150. Sotiriou SN, Orlova VV, Al-Fakhri N, Ihanus E, Economopoulou M, Isermann B et al. Lipoprotein (a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. FASEB J 2006; 20:559-561.
151. Hajjar KA, Jacovina AT. Modulation of annexin II by homocysteine: implications for atherothrombosis. J In-vestig Med 1998; 46 (8): 364-369.
152. Hopkins PN, Wu LL, Hunt SC, James BC, Vincent GM, Williams RR. Lipoprotein (a) interactions with lipid and nonlipid risk factors in early familial coronary artery disease. Arterioscler Thromb Vasc Biol 1997; 17:2783-2792.
153. Valentine RJ, Kaplan HS, Green R, Jacobsen DW, Myers SI, Clagett GP. Lipoprotein (a), homocysteine, and hypercoagulable states in young men with premature peripheral atherosclerosis: a prospective, controlled analysis. J Vasc Surg. 1996; 23: 53-61.
154. Guven A, Inanc F, Kilinc M and Ekerbicer H. Plasma homocysteine and lipoprotein (a) levels in Turkish patients with metabolic syndrome. Heart and Vessels 2005; 20 (6): 290-295.
155. Laraqui A, Bennouar N, Meggouh F, Allami A, El Kadiri N, Benkouka F et al. Homocysteine, lipopro-tein (a): risk factors for coronary heart disease. Ann Biol Clin 2002; 60 (5): 549-557.