Abstract
Background: T‐lymphocytes are present in significant numbers in the atherosclerotic plaque, but their role in the progression and pathogenesis of coronary syndromes remains poorly understood.
Hypothesis: We sought to determine the relationship between T‐lymphocyte activation and ischemic heart disease by measuring plasma levels of cytokines related to T‐lymphocyte function in patients with stable and unstable angina.
Methods: Plasma levels of interleukin‐2 (IL‐2) and soluble IL‐2 receptor (sIL‐2R) were measured in 105 patients: 66 with stable angina, 24 with unstable angina, and 15 healthy controls. Patients who presented to the cardiac catheterization laboratory with unstable or stable anginal syndromes for coronary angiography or percutaneous coronary intervention enrolled in the study.
Results: Mean levels of IL‐2 were significantly higher in patients with stable angina than in those with unstable angina. The differences between stable angina and control groups, or between unstable angina and control groups, were not statistically significant. Mean levels of sIL‐2R were significantly higher in patients with stable angina than in either patients with unstable angina or control patients.
Conclusions: Levels of IL‐2 and sIL‐2 receptor are significantly elevated in patients with stable angina, but not in patients with unstable angina. The contribution of T‐lymphocytes to the development of both stable and unstable angina requires further investigation.
Keywords: interleukins, unstable angina, stable angina
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References
- 1. Davies MJ, Thomas AC: Plaque fissuring—the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 1985; 53: 363–373 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Fuster V: Mechanisms leading to myocardial infarction: Insights from studies of vascular biology. Circulation 1994; 90: 2126–2146 [DOI] [PubMed] [Google Scholar]
- 3. Yarnell JWG, Baker IA, Sweetnam PM: Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. Circulation 1991; 88: 836–844 [DOI] [PubMed] [Google Scholar]
- 4. van der Wal AC, Becker AE, van der Loos CM: Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994; 90: 36–44 [DOI] [PubMed] [Google Scholar]
- 5. Wang N, Tabas I, Winchester R: Interleukin‐8 is induced by cholesterol loading of macrophages and expressed by macrophage foam cells in human atheroma. J Biol Chem 1996; 271: 8837–8842 [DOI] [PubMed] [Google Scholar]
- 6. Serneri GGN, Abbate R, Gori AM: Transient intermittent lymphocyte activation is responsible for the instability of angina. Circulation 1992; 86: 790–797 [DOI] [PubMed] [Google Scholar]
- 7. Liuzzo G, Biasucci LM, Gallimore R: The prognostic value of C‐reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994; 331: 417–424 [DOI] [PubMed] [Google Scholar]
- 8. Biasucci LN, Vitelli A, Liuzzo G: Elevated levels of interleukin‐6 in unstable angina. Circulation 1996; 95: 874–877 [DOI] [PubMed] [Google Scholar]
- 9. Blum A, Sclarovsky S, Shohat B: T‐lymphocyte activation in stable angina pectoris and after percutaneous transluminal coronary angioplasty. Circulation 1995; 91: 20–22 [DOI] [PubMed] [Google Scholar]
- 10. Libby P, Hansson GK: Involvement of the immune system in human atherogenesis: Current knowledge and unanswered questions. Lab Invest 1991; 64: 5–15 [PubMed] [Google Scholar]
- 11. Hansson GK, Jonasson L, Seifert PS: Immune mechanisms in atherosclerosis. Arteriosclerosis 1989; 9: 567–578 [DOI] [PubMed] [Google Scholar]
- 12. Wang W, Chen HJ, Giedd KN: T‐cell lymphokines, interleukin‐4, and gamma interferon modulate the induction of vascular smooth muscle cell tissue plasminogen activator and migration by serum and platelet‐derived growth factor. Circ Res 1995; 77: 1095–1106 [DOI] [PubMed] [Google Scholar]
- 13. Wang W, Chen HJ, Schwartz A: T cell lymphokines modulate smooth muscle cell fibrinolysis and migration induced by basic fibroblast growth factor. Am J Physiol; Cell Physiol 1997; 272 (Cell Physiol 41): C392–C398 [DOI] [PubMed] [Google Scholar]
- 14. Hansson GK, Holm J, Jonasson L: Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol 1989; 135: 169–175 [PMC free article] [PubMed] [Google Scholar]
- 15. Stemme S, Holm J, Hansson GK: T lymphocytes in human atherosclerotic plaques are memory cells expressing CD45RO and the integrin VLA‐1. Arterioscler Thromb 1991; 12: 206–211 [DOI] [PubMed] [Google Scholar]
- 16. Weiss A: T lymphocyte activation In Fundamental Immunology (Ed. Paul WE.), p. 493, New York: Raven Press, 1993. [Google Scholar]
- 17. Rubin LA, Nelson DL: The soluble interleukin‐2 receptor: Biology, function, and clinical application. Ann Intern Med 1990; 113: 619–627 [DOI] [PubMed] [Google Scholar]
- 18. Hansson GK, Libby P: The role of the lymphocyte In Atherosclerosis and Coronary Artery Disease, p. 557–568 (Eds. Fuster V, Ross R, Topol EJ.). Philadelphia: Lippincott‐Raven Publishers, 1996. [Google Scholar]
- 19. Apostolopoulos J, Davenport P, Tipping PG: Interleukin‐8 production by macrophages from atheromatous plaques. Arterioscler Thromb Vasc Biol 1996; 16: 1007–1012 [DOI] [PubMed] [Google Scholar]
- 20. Galea J, Armstrong J, Gadsdon P: Interleukin‐1ß in coronary arteries of patients with ischemic heart disease. Arterioscler Thromb Vasc Biol 1992; 16: 1000–1006 [DOI] [PubMed] [Google Scholar]
- 21. Stemme S, Rymo L, Hannson G: Polyclonal origin of T‐lymphocytes in human atherosclerotic plaques. Lab Invest 1991; 65: 654–660 [PubMed] [Google Scholar]
- 22. Jonasson L, Holm J, Skalli O: Regional accumulation of T cells, macrophages, and smooth muscle cells in the human atJierosclerotic plaque. Arteriosclerosis 1986; 6: 131–138 [DOI] [PubMed] [Google Scholar]
- 23. van der Waal A, Piek J, de Boer O: Recent activation of the plaque immune response in coronary lesions underlying acute coronary syndromes. Heart 1998; 80: 14–18 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Maseri A: Inflammation, atherosclerosis, and ischemic events: Exploring the hidden side of the moon. N Engl J Med 1997; 336: 1014–1015 [DOI] [PubMed] [Google Scholar]
- 25. Geng YJ, Hansson GK: Interferon‐g inhibits scavenger receptor expression and foam cell formation in human monocyte‐derived macrophages. Arterioscler Thromb Vasc Biol 1995; 15: 949–955 7541294 [Google Scholar]
- 26. Oppenheimer MJ, Oram JF, Bierman EL: Upregulation of high density lipoprotein receptor activity by interferon‐g associated with inhibition of cell proliferation. J Biol Chem 1988; 263: 19318–19323 [PubMed] [Google Scholar]
- 27. MacIsaac AI, Thomas JD, Topol EJ: Toward the quiescent coronary plaque. J Am Coll Cardiol 1993; 22: 1228–1241 [DOI] [PubMed] [Google Scholar]
- 28. Peoples GE, Blotnick S, Takahashi K: T lymphocytes that infiltrate tumors and atherosclerotic plaques produce heparin‐binding epidermal growth factor‐like growth factor and basic fibroblast growth factor: A potential pathologic role. Proc Natl Acad Sci 1995; 92: 6547–6551 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Hannson GK, Holm J, Holm S: T lymphocytes inhibit the vascular response to injury. Proc Natl Acad Sci USA 1991; 88: 10530–10534 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Ekre HP, Naparstek Y, Lider O: Anti‐inflammatory effects of heparin and its derivatives: Inhibition of complement and of lymphocyte migration In Heparin and Related Polysaccharides, p. 329–340 (Ed. Lane DA.). New York: Plenum Press, 1992. [DOI] [PubMed] [Google Scholar]
- 31. Caligiuri G, Liuzzo G, Biasucci LM: Immune system activation follows inflammation in unstable angina: Pathogenetic implications. J Am Coll Cardiol 1998; 32: 1295–1304 [DOI] [PubMed] [Google Scholar]