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Understanding Vulnerable Plaques: Current Status and Future Directions

  • Lee, Kwan Yong (Cardiovascular Center and Cardiology Division, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Chang, Kiyuk (Cardiovascular Center and Cardiology Division, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea)
  • Received : 2019.07.03
  • Accepted : 2019.10.07
  • Published : 2019.12.31

Abstract

The main cause of acute myocardial infarction is plaque rupture accompanied by superimposed coronary thrombosis. Thin-cap fibroatheromas (TCFAs) have been suggested as a type of lesion with a vulnerability that can cause plaque rupture. However, not only the existence of a TCFA but also the fine and complex interactions of other anatomical and hemodynamic factors, such as microcalcification in the fibrous cap, cholesterol crystal-induced inflammasome activation, the apoptosis of intraplaque macrophages, and endothelial shear stress distribution should precede a clinical event caused by plaque rupture. Recent studies are being conducted to identify these mechanisms through molecular imaging and hemodynamic assessment using computational fluid dynamics, which will result in better clinical results through selective coronary interventions.

Keywords

Acknowledgement

This research were partly supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03036436) and the Bio & Medical Technology Development Program of the NRF funded by the Ministry of Science & ICT (NRF-2017M3A9D8061157).

References

  1. Schuurman AS, Vroegindewey MM, Kardys I, et al. Prognostic value of intravascular ultrasound in patients with coronary artery disease. J Am Coll Cardiol 2018;72:2003-11. https://doi.org/10.1016/j.jacc.2018.08.2140
  2. Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on coronary plaque composition. J Am Coll Cardiol 2018;72:2012-21. https://doi.org/10.1016/j.jacc.2018.06.078
  3. Arbab-Zadeh A, Fuster V. The myth of the "vulnerable plaque": transitioning from a focus on individual lesions to atherosclerotic disease burden for coronary artery disease risk assessment. J Am Coll Cardiol 2015;65:846-55. https://doi.org/10.1016/j.jacc.2014.11.041
  4. Tian J, Ren X, Vergallo R, et al. Distinct morphological features of ruptured culprit plaque for acute coronary events compared to those with silent rupture and thin-cap fibroatheroma: a combined optical coherence tomography and intravascular ultrasound study. J Am Coll Cardiol 2014;63:2209-16. https://doi.org/10.1016/j.jacc.2014.01.061
  5. Toutouzas K, Karanasos A, Tsiamis E, et al. New insights by optical coherence tomography into the differences and similarities of culprit ruptured plaque morphology in non-ST-elevation myocardial infarction and ST-elevation myocardial infarction. Am Heart J 2011;161:1192-9. https://doi.org/10.1016/j.ahj.2011.03.005
  6. deFilippi CR, de Lemos JA, Tkaczuk AT, et al. Physical activity, change in biomarkers of myocardial stress and injury, and subsequent heart failure risk in older adults. J Am Coll Cardiol 2012;60:2539-47. https://doi.org/10.1016/j.jacc.2012.08.1006
  7. Otsuka F, Sakakura K, Yahagi K, Joner M, Virmani R. Has our understanding of calcification in human coronary atherosclerosis progressed? Arterioscler Thromb Vasc Biol 2014;34:724-36. https://doi.org/10.1161/ATVBAHA.113.302642
  8. Vedre A, Pathak DR, Crimp M, Lum C, Koochesfahani M, Abela GS. Physical factors that trigger cholesterol crystallization leading to plaque rupture. Atherosclerosis 2009;203:89-96. https://doi.org/10.1016/j.atherosclerosis.2008.06.027
  9. Kietselaer BL, Reutelingsperger CP, Heidendal GA, et al. Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis. N Engl J Med 2004;350:1472-3.
  10. Pedrigi RM, de Silva R, Bovens SM, Mehta VV, Petretto E, Krams R. Thin-cap fibroatheroma rupture is associated with a fine interplay of shear and wall stress. Arterioscler Thromb Vasc Biol 2014;34:2224-31. https://doi.org/10.1161/ATVBAHA.114.303426
  11. Herrick JB. Landmark article (JAMA 1912). Clinical features of sudden obstruction of the coronary arteries. By James B. Herrick. JAMA 1983;250:1757-65. https://doi.org/10.1001/jama.1983.03340130075039
  12. Clark E, Graef I, Chasis H. Thrombosis of the aorta and coronary arteries with specific reference to the "fibrinoid" lesions. Arch Pathol (Chic) 1936;22:183-212.
  13. Constantinides P. Plaque fissures in human coronary thrombosis. Fed Prox 1964;23:443.
  14. Davies MJ. Stability and instability: two faces of coronary atherosclerosis. The Paul Dudley White Lecture 1995. Circulation 1996;94:2013-20. https://doi.org/10.1161/01.CIR.94.8.2013
  15. Jenniskens M, Langouche L, Van den Berghe G. Cholestatic alterations in the critically ill: some new light on an old problem. Chest 2018;153:733-43. https://doi.org/10.1016/j.chest.2017.08.018
  16. Schaar JA, Muller JE, Falk E, et al. Terminology for high-risk and vulnerable coronary artery plaques. Report of a meeting on the vulnerable plaque, June 17 and 18, 2003, Santorini, Greece. Eur Heart J 2004;25:1077-82. https://doi.org/10.1016/j.ehj.2004.01.002
  17. Kolodgie FD, Burke AP, Farb A, et al. The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes. Curr Opin Cardiol 2001;16:285-92. https://doi.org/10.1097/00001573-200109000-00006
  18. Kolodgie FD, Virmani R, Burke AP, et al. Pathologic assessment of the vulnerable human coronary plaque. Heart 2004;90:1385-91. https://doi.org/10.1136/hrt.2004.041798
  19. Beckman JA, Ganz J, Creager MA, Ganz P, Kinlay S. Relationship of clinical presentation and calcification of culprit coronary artery stenoses. Arterioscler Thromb Vasc Biol 2001;21:1618-22. https://doi.org/10.1161/hq0901.095554
  20. Karanasos A, Ligthart JM, Witberg KT, Regar E. Calcified nodules: an underrated mechanism of coronary thrombosis? JACC Cardiovasc Imaging 2012;5:1071-2. https://doi.org/10.1016/j.jcmg.2012.04.010
  21. Ehara S, Kobayashi Y, Yoshiyama M, et al. Spotty calcification typifies the culprit plaque in patients with acute myocardial infarction: an intravascular ultrasound study. Circulation 2004;110:3424-9. https://doi.org/10.1161/01.CIR.0000148131.41425.E9
  22. Motoyama S, Kondo T, Sarai M, et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol 2007;50:319-26. https://doi.org/10.1016/j.jacc.2007.03.044
  23. Kivimaki M, Pentti J, Ferrie JE, et al. Work stress and risk of death in men and women with and without cardiometabolic disease: a multicohort study. Lancet Diabetes Endocrinol 2018;6:705-13. https://doi.org/10.1016/S2213-8587(18)30140-2
  24. Vengrenyuk Y, Carlier S, Xanthos S, et al. A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc Natl Acad Sci U S A 2006;103:14678-83. https://doi.org/10.1073/pnas.0606310103
  25. Kashiwagi M, Liu L, Chu KK, et al. Feasibility of the assessment of cholesterol crystals in human macrophages using micro optical coherence tomography. PLoS One 2014;9:e102669. https://doi.org/10.1371/journal.pone.0102669
  26. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119-31. https://doi.org/10.1056/NEJMoa1707914
  27. Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol 2010;10:36-46. https://doi.org/10.1038/nri2675
  28. Tabas I. The role of endoplasmic reticulum stress in the progression of atherosclerosis. Circ Res 2010;107:839-50. https://doi.org/10.1161/CIRCRESAHA.110.224766
  29. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell 2011;145:341-55. https://doi.org/10.1016/j.cell.2011.04.005
  30. Sinusas AJ, Bengel F, Nahrendorf M, et al. Multimodality cardiovascular molecular imaging, part I. Circ Cardiovasc Imaging 2008;1:244-56. https://doi.org/10.1161/CIRCIMAGING.108.824359
  31. Nahrendorf M, Sosnovik DE, French BA, et al. Multimodality cardiovascular molecular imaging, part II. Circ Cardiovasc Imaging 2009;2:56-70. https://doi.org/10.1161/CIRCIMAGING.108.839092
  32. Jaffer FA, Nahrendorf M, Sosnovik D, Kelly KA, Aikawa E, Weissleder R. Cellular imaging of inflammation in atherosclerosis using magnetofluorescent nanomaterials. Mol Imaging 2006;5:85-92.
  33. Hwang BH, Kim MH, Chang K. Molecular imaging of high-risk atherosclerotic plaques: is it clinically translatable? Korean Circ J 2011;41:497-502. https://doi.org/10.4070/kcj.2011.41.9.497
  34. Hlatky MA, Douglas PS, Cook NL, et al. Future directions for cardiovascular disease comparative effectiveness research: report of a workshop sponsored by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol 2012;60:569-80. https://doi.org/10.1016/j.jacc.2011.12.057
  35. Kubo T, Maehara A, Mintz GS, et al. The dynamic nature of coronary artery lesion morphology assessed by serial virtual histology intravascular ultrasound tissue characterization. J Am Coll Cardiol 2010;55:1590-7. https://doi.org/10.1016/j.jacc.2009.07.078
  36. Perlini S, Meyer TE, Foex P. Effects of preload, afterload and inotropy on dynamics of ischemic segmental wall motion. J Am Coll Cardiol 1997;29:846-55. https://doi.org/10.1016/S0735-1097(96)00569-4
  37. Chatzizisis YS, Baker AB, Sukhova GK, et al. Augmented expression and activity of extracellular matrixdegrading enzymes in regions of low endothelial shear stress colocalize with coronary atheromata with thin fibrous caps in pigs. Circulation 2011;123:621-30. https://doi.org/10.1161/CIRCULATIONAHA.110.970038
  38. Chatzizisis YS, Jonas M, Coskun AU, et al. Prediction of the localization of high-risk coronary atherosclerotic plaques on the basis of low endothelial shear stress: an intravascular ultrasound and histopathology natural history study. Circulation 2008;117:993-1002. https://doi.org/10.1161/CIRCULATIONAHA.107.695254
  39. Koskinas KC, Sukhova GK, Baker AB, et al. Thin-capped atheromata with reduced collagen content in pigs develop in coronary arterial regions exposed to persistently low endothelial shear stress. Arterioscler Thromb Vasc Biol 2013;33:1494-504. https://doi.org/10.1161/ATVBAHA.112.300827
  40. Stone PH, Saito S, Takahashi S, et al. Prediction of progression of coronary artery disease and clinical outcomes using vascular profiling of endothelial shear stress and arterial plaque characteristics: the PREDICTION Study. Circulation 2012;126:172-81. https://doi.org/10.1161/CIRCULATIONAHA.112.096438
  41. Vergallo R, Papafaklis MI, Yonetsu T, et al. Endothelial shear stress and coronary plaque characteristics in humans: combined frequency-domain optical coherence tomography and computational fluid dynamics study. Circ Cardiovasc Imaging 2014;7:905-11. https://doi.org/10.1161/CIRCIMAGING.114.001932
  42. Phinikaridou A, Hua N, Pham T, Hamilton JA. Regions of low endothelial shear stress colocalize with positive vascular remodeling and atherosclerotic plaque disruption: an in vivo magnetic resonance imaging study. Circ Cardiovasc Imaging 2013;6:302-10. https://doi.org/10.1161/CIRCIMAGING.112.000176
  43. Koskinas KC, Chatzizisis YS, Baker AB, Edelman ER, Stone PH, Feldman CL. The role of low endothelial shear stress in the conversion of atherosclerotic lesions from stable to unstable plaque. Curr Opin Cardiol 2009;24:580-90. https://doi.org/10.1097/HCO.0b013e328331630b
  44. Kwak BR, Back M, Bochaton-Piallat ML, et al. Biomechanical factors in atherosclerosis: mechanisms and clinical implications. Eur Heart J 2014;35:3013-20. https://doi.org/10.1093/eurheartj/ehu353
  45. Kumar A, Thompson EW, Lefieux A, et al. High coronary shear stress in patients with coronary artery disease predicts myocardial infarction. J Am Coll Cardiol 2018;72:1926-35. https://doi.org/10.1016/j.jacc.2018.07.075