Arindam Maitra, Jayashree Shanker, Debabrata Dash, Prathima Arvind, Vijay V. Kakkar In conclusion, the present study provides early leads on the differential pattern in the expression levels of TLR-2, TLR-4 and TLR-9 genes in CAD patients with strong familial predisposition to CVD. This is in line with the emerging paradigm that atherosclerosis is a pathogen-mediated immuno- modulatory disease. Further work is required to understand the true profile of TLRs, their correlation with presence of infection and other inflammatory biomarkers, as well as their functional relevance to the pathology of coronary artery disease in Asian Indians. Acknowledgments We thank the Trustees of TRI India and London for their support and encouragement. We are very grateful to the Tata Social Welfare Trust, the Department of Biotechnology, Garfield Weston Foundation and the Elizabeth & Emmanuel Kaye Foundation for the financial support extended to the Indian Atherosclerosis Research Study and the Thrombosis Research Institute India. We thank the doctors at Narayana Hrudayalaya and other hospitals in Bangalore and the Asian Heart Institute and Research Center in Mumbai for providing clinical assistance. We appreciate the efforts of the clinical staff, the data entry team and the administrative members of TRI India and London. We profusely thank the study participants for their voluntary participation in our study. R e f e r e n c e s 1. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352: 1685-95. 2. Nilsson J, Hansson GK, Shah PK. Immunomodulation of atherosclerosis: implications for vaccine development. Arterioscler Thromb Vasc Biol 2005; 25: 18-28. 3. Curtiss LK, Tobias PS. Emerging role of Toll-like receptors in atherosclerosis. J Lipid Res 2009; 50 Suppl: S340-5. 4. Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001; 2: 675-80. 5. Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol 2003; 21: 335-76. 6. Brikos C, O'Neill LA. Signalling of toll-like receptors. Handb Exp Pharmacol 2008; 183: 21-50. 7. Oude Nijhuis MM, van Keulen JK, Pasterkamp G, Quax PH, de Kleijn DP. Activation of the innate immune system in atherosclerotic disease. Curr Pharm Des 2007; 13: 983-94. 8. Frantz S, Ertl G, Bauersachs J. Mechanisms of disease: Toll-like receptors in cardiovascular disease. Nat Clin Pract Cardiovasc Med 2007; 4: 444-54. 9. Tobias PS, Curtiss LK. Toll-like receptors in atherosclerosis. Biochem Soc Trans 2007; 35: 1453-5. 10. Edfeldt K, Swedenborg J, Hansson GK, Yan ZQ. Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation 2002; 105: 1158-61. 11. Ishikawa Y, Satoh M, Itoh T, et al. Local expression of Toll- like receptor 4 at the site of ruptured plaques in patients with acute myocardial infarction. Clin Sci (Lond) 2008; 115: 133-40. 12. Satoh M, Ishikawa Y, Minami Y, Takahashi Y, Nakamura M. Role of Toll like receptor signaling pathway in ischemic coronary artery disease. Front Biosci 2008; 13: 6708-15. 13. Takeda K, Akira S. TLR signaling pathways. Semin Immunol 2004; 16: 3-9. 14. Hansson GK, Nilsson J. Vaccination against athero- sclerosis? Induction of atheroprotective immunity. Semin Immunopathol 2009; 31: 95-101. 15. Bhattacharjee RN, Akira S. Modifying toll-like receptor 9 signaling for therapeutic use. Mini Rev Med Chem 2006; 6: 287-91. 16. Kanzler H, Barrat FJ, Hessel EM, Coffman RL. Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nat Med 2007; 13: 552-9. 17. Monaco C, Gregan SM, Navin TJ, et al. Toll-like receptor-2 mediates inflammation and matrix degradation in human atherosclerosis. Circulation 2009; 120: 2462-9. 18. Kumar NK. Bioethics activities in India. East Mediterr Health J 2006; 12 Suppl 1: S56-65. 19. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001; 29: e45. 20. Epstein SE. The multiple mechanisms by which infection may contribute to atherosclerosis development and course. Circ Res 2002; 90: 2-4. 21. Epstein SE, Zhou YF, Zhu J. Infection and atherosclerosis: emerging mechanistic paradigms. Circulation 1999; 100: e20-8. 22. Deniset JF, Cheung PK, Dibrov E, et al. Chlamydophila pneumoniae infection leads to smooth muscle cell proliferation and thickening in the coronary artery without contributions from a host immune response. Am J Pathol 2010; 176: 1028-37. 23. Michelsen KS, Doherty TM, Shah PK, Arditi M. TLR signaling: an emerging bridge from innate immunity to atherogenesis. J Immunol 2004; 173: 5901-7. 24. Miller YI, Viriyakosol S, Worrall DS, et al. Toll-like receptor 4-dependent and -independent cytokine secretion induced by minimally oxidized low-density lipoprotein in macrophages. Arterioscler Thromb Vasc Biol 2005; 25: 1213-9. 25. Walton KA, Cole AL, Yeh M, et al. Specific phospholipid oxidation products inhibit ligand activation of toll-like receptors 4 and 2. Arterioscler Thromb Vasc Biol 2003; 23: 1197-203. 26. Bulut Y, Faure E, Thomas L, et al. Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88- dependent pathway. J Immunol 2002; 168: 1435-40. 27. Vabulas RM, Ahmad-Nejad P, da Costa C, et al. Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem 2001; 276: 31332-9. 28. Xu Q. Infections, heat shock proteins, and atherosclerosis. Curr Opin Cardiol 2003; 18: 245-52. 29. Ionita MG, Arslan F, de Kleijn DP, Pasterkamp G. Endogenous inflammatory molecules engage Toll-like receptors in cardiovascular disease. J Innate Immun 2010; 2: 307-15. 786 Arch Med Sci 5, October / 2011