Key Points
-
The aetiology of luminal thrombosis in native coronary arteries is predominately plaque rupture, but can also be surface erosion and, least frequently, calcified nodules
-
The main precursor lesion with potential for rupture is identified as a 'vulnerable plaque' or 'thin-cap fibroatheroma', and is considered an appropriate therapeutic target for patients at risk of future coronary events
-
Native coronary disease develops over decades, whereas accelerated atherosclerosis is observed in saphenous vein grafts and in stents within months to years
-
In saphenous vein grafts and stents, accelerated atherosclerosis is likely to develop from resident macrophage-derived foam cells, which undergo apoptosis and form necrotic cores; pathological intimal thickening is rarely observed
-
By contrast, native coronary disease is thought to progress from lipid pools associated with pathological intimal thickening; necrotic cores arise from macrophage infiltration of these lipid pools
-
Important morphological identifiers of accelerated plaque progression include macrophage foam cells, intraplaque haemorrhage, and fibrous cap thickness
Abstract
Plaque rupture, usually of a precursor lesion known as a 'vulnerable plaque' or 'thin-cap fibroatheroma', is the leading cause of thrombosis. Less-frequent aetiologies of coronary thrombosis are erosion, observed with greatest incidence in women aged <50 years, and eruptive calcified nodules, which are occasionally identified in older individuals. Various treatments for patients with coronary artery disease, such as CABG surgery and interventional therapies, have led to accelerated atherosclerosis. These processes occur within months to years, compared with the decades that it generally takes for native disease to develop. Morphological identifiers of accelerated atherosclerosis include macrophage-derived foam cells, intraplaque haemorrhage, and thin fibrous cap. Foam-cell infiltration can be observed within 1 year of a saphenous vein graft implantation, with subsequent necrotic core formation and rupture ensuing after 7 years in over one-third of patients. Neoatherosclerosis occurs early and with greater prevalence in drug-eluting stents than in bare-metal stents and, although rare, complications of late stent thrombosis from rupture are associated with high mortality. Comparison of lesion progression in native atherosclerotic disease, atherosclerosis in saphenous vein grafts, and in-stent neoatherosclerosis provides insight into the pathogenesis of atheroma formation in natural and iatrogenic settings.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Laslett, L. J. et al. The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology. J. Am. Coll. Cardiol. 60 (Suppl.), S1–S49 (2012).
Fihn, S. D. et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 126, e354–e471 (2012).
Lloyd-Jones, D. et al. Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation 121, e46–e215 (2010).
Heron, M. Deaths: leading causes for 2010. Natl Vital Stat. Rep. 62, 1–96 (2013).
Lloyd-Jones, D. M., Larson, M. G., Beiser, A. & Levy, D. Lifetime risk of developing coronary heart disease. Lancet 353, 89–92 (1999).
Serruys, P. W. et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N. Engl. J. Med. 360, 961–972 (2009).
Yi, G., Shine, B., Rehman, S. M., Altman, D. G. & Taggart, D. P. Effect of bilateral internal mammary artery grafts on long-term survival: a meta-analysis approach. Circulation 130, 539–545 (2014).
Sabik, J. F. 3rd, Lytle, B. W., Blackstone, E. H., Houghtaling, P. L. & Cosgrove, D. M. Comparison of saphenous vein and internal thoracic artery graft patency by coronary system. Ann. Thorac. Surg. 79, 544–551 (2005).
Fitzgibbon, G. M. et al. Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years. J. Am. Coll. Cardiol. 28, 616–626 (1996).
Chesebro, J. H. et al. Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations. N. Engl. J. Med. 310, 209–214 (1984).
Bourassa, M. G. et al. Long-term fate of bypass grafts: the Coronary Artery Surgery Study (CASS) and Montreal Heart Institute experiences. Circulation 72, V71–V78 (1985).
Finn, A. V. et al. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation 115, 2435–2441 (2007).
Joner, M. et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J. Am. Coll. Cardiol. 48, 193–202 (2006).
Nakazawa, G. et al. The pathology of neoatherosclerosis in human coronary implants bare-metal and drug-eluting stents. J. Am. Coll. Cardiol. 57, 1314–1322 (2011).
Otsuka, F. et al. Pathology of second-generation everolimus-eluting stents versus first-generation sirolimus- and paclitaxel-eluting stents in humans. Circulation 129, 211–223 (2014).
Virmani, R., Kolodgie, F. D., Burke, A. P., Farb, A. & Schwartz, S. M. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 20, 1262–1275 (2000).
Ross, R. & Glomset, J. A. The pathogenesis of atherosclerosis (first of two parts). N. Engl. J. Med. 295, 369–377 (1976).
Ross, R. The pathogenesis of atherosclerosis—an update. N. Engl. J. Med. 314, 488–500 (1986).
Ross, R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801–809 (1993).
Libby, P. Inflammation in atherosclerosis. Nature 420, 868–874 (2002).
Hansson, G. K., Libby, P., Schonbeck, U. & Yan, Z. Q. Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ. Res. 91, 281–291 (2002).
Hansson, G. K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 352, 1685–1695 (2005).
Fuster, V., Badimon, L., Badimon, J. J. & Chesebro, J. H. The pathogenesis of coronary artery disease and the acute coronary syndromes (1). N. Engl. J. Med. 326, 242–250 (1992).
Fuster, V. Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. Circulation 90, 2126–2146 (1994).
Stary, H. C. et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler. Thromb. Vasc. Biol. 15, 1512–1531 (1995).
Davies, M. J. & Thomas, A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N. Engl. J. Med. 310, 1137–1140 (1984).
Falk, E., Nakano, M., Bentzon, J. F., Finn, A. V. & Virmani, R. Update on acute coronary syndromes: the pathologists' view. Eur. Heart J. 34, 719–728 (2013).
Stary, H. C. et al. A definition of the intima of human arteries and of its atherosclerosis-prone regions. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler. Thromb. 12, 120–134 (1992).
Kolodgie, F. D. et al. Intraplaque hemorrhage and progression of coronary atheroma. N. Engl. J. Med. 349, 2316–2325 (2003).
Nakashima, Y., Chen, Y. X., Kinukawa, N. & Sueishi, K. Distributions of diffuse intimal thickening in human arteries: preferential expression in atherosclerosis-prone arteries from an early age. Virchows Arch. 441, 279–288 (2002).
Ikari, Y., McManus, B. M., Kenyon, J. & Schwartz, S. M. Neonatal intima formation in the human coronary artery. Arterioscler. Thromb. Vasc. Biol. 19, 2036–2040 (1999).
McGill, H. C. Jr et al. Relation of a postmortem renal index of hypertension to atherosclerosis and coronary artery size in young men and women. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler. Thromb. Vasc. Biol. 18, 1108–1118 (1998).
Fan, J. & Watanabe, T. Inflammatory reactions in the pathogenesis of atherosclerosis. J. Atheroscler. Thromb. 10, 63–71 (2003).
Aikawa, M. et al. Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. Circulation 97, 2433–2444 (1998).
Velican, C. Relationship between regional aortic susceptibility to atherosclerosis and macromolecular structural stability. J. Atheroscler. Res. 9, 193–201 (1969).
Velican, C. A dissecting view on the role of the fatty streak in the pathogenesis of human atherosclerosis: culprit or bystander? Med. Interne 19, 321–337 (1981).
McGill, H. C. Jr et al. Effects of coronary heart disease risk factors on atherosclerosis of selected regions of the aorta and right coronary artery. PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth. Arterioscler. Thromb. Vasc. Biol. 20, 836–845 (2000).
Kockx, M. M. et al. Luminal foam cell accumulation is associated with smooth muscle cell death in the intimal thickening of human saphenous vein grafts. Circulation 94, 1255–1262 (1996).
Nakashima, Y., Fujii, H., Sumiyoshi, S., Wight, T. N. & Sueishi, K. Early human atherosclerosis: accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration. Arterioscler. Thromb. Vasc. Biol. 27, 1159–1165 (2007).
Williams, K. J. Interactions of lipoproteins with proteoglycans. Methods Mol. Biol. 171, 457–477 (2001).
Nakashima, Y., Wight, T. N. & Sueishi, K. Early atherosclerosis in humans: role of diffuse intimal thickening and extracellular matrix proteoglycans. Cardiovasc. Res. 79, 14–23 (2008).
Gustafsson, M. et al. Retention of low-density lipoprotein in atherosclerotic lesions of the mouse: evidence for a role of lipoprotein lipase. Circ. Res. 101, 777–783 (2007).
Radhakrishnamurthy, B., Tracy, R. E., Dalferes, E. R. Jr & Berenson, G. S. Proteoglycans in human coronary arteriosclerotic lesions. Exp. Mol. Pathol. 65, 1–8 (1998).
Smith, E. B. & Slater, R. S. The microdissection of large atherosclerotic plaques to give morphologically and topographically defined fractions for analysis. 1. The lipids in the isolated fractions. Atherosclerosis 15, 37–56 (1972).
Tulenko, T. N., Chen, M., Mason, P. E. & Mason, R. P. Physical effects of cholesterol on arterial smooth muscle membranes: evidence of immiscible cholesterol domains and alterations in bilayer width during atherogenesis. J. Lipid Res. 39, 947–956 (1998).
Otsuka, F., Sakakura, K., Yahagi, K., Joner, M. & Virmani, R. Has our understanding of calcification in human coronary atherosclerosis progressed? Arterioscler. Thromb. Vasc. Biol. 34, 724–736 (2014).
Bogels, M. et al. Carcinoma origin dictates differential skewing of monocyte function. Oncoimmunology 1, 798–809 (2012).
Wight, T. N., Kang, I. & Merrilees, M. J. Versican and the control of inflammation. Matrix Biol. 35, 152–161 (2014).
Wight, T. N., Kinsella, M. G., Evanko, S. P., Potter-Perigo, S. & Merrilees, M. J. Versican and the regulation of cell phenotype in disease. Biochim. Biophys. Acta 1840, 2441–2451 (2014).
Chang, M. Y. et al. Monocyte-to-macrophage differentiation: synthesis and secretion of a complex extracellular matrix. J. Biol. Chem. 287, 14122–14135 (2012).
Otsuka, F. et al. Natural progression of atherosclerosis from pathologic intimal thickening to late fibroatheroma in human coronary arteries: a pathology study. Atherosclerosis 241, 772–782 (2015).
Stupka, N. et al. Versican processing by a disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats proteinases-5 and -15 facilitates myoblast fusion. J. Biol. Chem. 288, 1907–1917 (2013).
Virmani, R., Joner, M. & Sakakura, K. Recent highlights of ATVB: calcification. Arterioscler. Thromb. Vasc. Biol. 34, 1329–1332 (2014).
Sluimer, J. C. et al. Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage. J. Am. Coll. Cardiol. 53, 1517–1527 (2009).
Tabas, I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat. Rev. Immunol. 10, 36–46 (2010).
Johnson, J. L. et al. Relationship of MMP-14 and TIMP-3 expression with macrophage activation and human atherosclerotic plaque vulnerability. Mediators Inflamm. 2014, 276457 (2014).
Lee, C. W. et al. Comparison of ADAMTS-1, -4 and -5 expression in culprit plaques between acute myocardial infarction and stable angina. J. Clin. Pathol. 64, 399–404 (2011).
Edsfeldt, A. et al. Impaired fibrous repair: a possible contributor to atherosclerotic plaque vulnerability in patients with type II diabetes. Arterioscler. Thromb. Vasc. Biol. 34, 2143–2150 (2014).
Virmani, R., Burke, A. P., Farb, A. & Kolodgie, F. D. Pathology of the vulnerable plaque. J. Am. Coll. Cardiol. 47, C13–C18 (2006).
Burke, A. P. et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N. Engl. J. Med. 336, 1276–1282 (1997).
Burke, A. P., Virmani, R., Galis, Z., Haudenschild, C. C. & Muller, J. E. 34th Bethesda Conference: Task force #2—What is the pathologic basis for new atherosclerosis imaging techniques? J. Am. Coll. Cardiol. 41, 1874–1886 (2003).
Farb, A. et al. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation 93, 1354–1363 (1996).
Narula, J. et al. Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. J. Am. Coll. Cardiol. 61, 1041–1051 (2013).
van der Wal, A. C., Becker, A. E., van der Loos, C. M. & Das, P. K. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 89, 36–44 (1994).
Yahagi, K., Davis, H. R., Arbustini, E. & Virmani, R. Sex differences in coronary artery disease: pathological observations. Atherosclerosis 239, 260–267 (2015).
Jia H. et al. In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography. J. Am. Coll. Cardiol. 62, 1748–1758 (2013).
Burke, A. P. et al. Plaque rupture and sudden death related to exertion in men with coronary artery disease. JAMA 281, 921–926 (1999).
Sukhova, G. K. et al. Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. Circulation 99, 2503–2509 (1999).
Gijsen, F. J. et al. Strain distribution over plaques in human coronary arteries relates to shear stress. Am. J. Physiol. Heart Circ. Physiol. 295, H1608–H1614 (2008).
Kolodgie, F. D. et al. Localization of apoptotic macrophages at the site of plaque rupture in sudden coronary death. Am. J. Pathol. 157, 1259–1268 (2000).
Vengrenyuk, Y. et al. A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc. Natl Acad. Sci. USA 103, 14678–14683 (2006).
Yahagi, K. et al. Multiple simultaneous plaque erosion in 3 coronary arteries. JACC Cardiovasc. Imaging 7, 1172–1174 (2014).
Burke, A. P., Kolodgie, F. D., Farb, A., Weber, D. & Virmani, R. Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation 105, 297–303 (2002).
Kolodgie, F. D. et al. Differential accumulation of proteoglycans and hyaluronan in culprit lesions: insights into plaque erosion. Arterioscler. Thromb. Vasc. Biol. 22, 1642–1648 (2002).
Burke, A. P. et al. Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. Circulation 97, 2110–2116 (1998).
Kramer, M. C. et al. Relationship of thrombus healing to underlying plaque morphology in sudden coronary death. J. Am. Coll. Cardiol. 55, 122–132 (2010).
Schwartz, R. S. et al. Microemboli and microvascular obstruction in acute coronary thrombosis and sudden coronary death: relation to epicardial plaque histopathology. J. Am. Coll. Cardiol. 54, 2167–2173 (2009).
Mann, J. & Davies, M. J. Mechanisms of progression in native coronary artery disease: role of healed plaque disruption. Heart 82, 265–268 (1999).
Sakakura, K. et al. Comparison of pathology of chronic total occlusion with and without coronary artery bypass graft. Eur. Heart J. 35, 1683–1693 (2014).
Burke, A. P. et al. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation 103, 934–940 (2001).
Constantinides, P. Coronary thrombosis linked to fissure in atherosclerotic vessel wall. JAMA 188 (Suppl.), 35–37 (1964).
Davies, M. J. & Thomas, A. C. Plaque fissuring—the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br. Heart J. 53, 363–373 (1985).
Kumamoto, M., Nakashima, Y. & Sueishi, K. Intimal neovascularization in human coronary atherosclerosis: its origin and pathophysiological significance. Hum. Pathol. 26, 450–456 (1995).
Tabas, I. Consequences of cellular cholesterol accumulation: basic concepts and physiological implications. J. Clin. Invest. 110, 905–911 (2002).
Virmani, R. et al. Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage. Arterioscler. Thromb. Vasc. Biol. 25, 2054–2061 (2005).
Virmani, R., Narula, J. & Farb, A. When neoangiogenesis ricochets. Am. Heart J. 136, 937–939 (1998).
Mulligan-Kehoe, M. J. & Simons, M. Vasa vasorum in normal and diseased arteries. Circulation 129, 2557–2566 (2014).
Takaya, N. et al. Presence of intraplaque hemorrhage stimulates progression of carotid atherosclerotic plaques: a high-resolution magnetic resonance imaging study. Circulation 111, 2768–2775 (2005).
Chistiakov, D. A., Orekhov, A. N. & Bobryshev, Y. V. Contribution of neovascularization and intraplaque haemorrhage to atherosclerotic plaque progression and instability. Acta Physiol. (Oxf.) 213, 539–553 (2015).
Friedrich, G. J. et al. Detection of intralesional calcium by intracoronary ultrasound depends on the histologic pattern. Am. Heart J. 128, 435–441 (1994).
Burke, A. P. et al. Pathophysiology of calcium deposition in coronary arteries. Herz 26, 239–244 (2001).
Burke, A. P., Taylor, A., Farb, A., Malcom, G. T. & Virmani, R. Coronary calcification: insights from sudden coronary death victims. Z. Kardiol. 89 (Suppl. 2), 49–53 (2000).
Erbel, R. et al. Coronary risk stratification, discrimination, and reclassification improvement based on quantification of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall study. J. Am. Coll. Cardiol. 56, 1397–1406 (2010).
Burke, A. P., Farb, A., Malcom, G. & Virmani, R. Effect of menopause on plaque morphologic characteristics in coronary atherosclerosis. Am. Heart J. 141, S58–S62 (2001).
Watson, K. E. et al. Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation 96, 1755–1760 (1997).
Keso, T. et al. Polymorphisms within the tumor necrosis factor locus and prevalence of coronary artery disease in middle-aged men. Atherosclerosis 154, 691–697 (2001).
Spring, B. et al. Healthy lifestyle change and subclinical atherosclerosis in young adults: Coronary Artery Risk Development in Young Adults (CARDIA) study. Circulation 130, 10–17 (2014).
Burke, A. P., Kolodgie, F. D., Farb, A. & Virmani, R. in The Vulnerable Atherosclerotic Plaque: Strategies for Diagnosis and Management (eds Virmani, R., Narula, J., Leon, M. B. & Willerson, J. T.) 77–94 (Wiley-Blackwell, 2006).
Burke, A. P. et al. Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study. Arterioscler. Thromb. Vasc. Biol. 24, 1266–1271 (2004).
Walts, A. E., Fishbein, M. C. & Matloff, J. M. Thrombosed, ruptured atheromatous plaques in saphenous vein coronary artery bypass grafts: ten years' experience. Am. Heart J. 114, 718–723 (1987).
Yazdani, S. K. et al. Pathology of drug-eluting versus bare-metal stents in saphenous vein bypass graft lesions. JACC Cardiovasc. Interv. 5, 666–674 (2012).
Safian, R. D. Accelerated atherosclerosis in saphenous vein bypass grafts: a spectrum of diffuse plaque instability. Prog. Cardiovasc. Dis. 44, 437–448 (2002).
Shelton, M. E. et al. A comparison of morphologic and angiographic findings in long-term internal mammary artery and saphenous vein bypass grafts. J. Am. Coll. Cardiol. 11, 297–307 (1988).
Loop, F. D. et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N. Engl. J. Med. 314, 1–6 (1986).
Butany, J. W., David, T. E. & Ojha, M. Histological and morphometric analyses of early and late aortocoronary vein grafts and distal anastomoses. Can. J. Cardiol. 14, 671–677 (1998).
Peykar, S., Angiolillo, D. J., Bass, T. A. & Costa, M. A. Saphenous vein graft disease. Minerva Cardioangiologica 52, 379–390 (2004).
Waller, B. F. & Roberts, W. C. Remnant saphenous veins after aortocoronary bypass grafting: analysis of 3,394 centimeters of unused vein from 402 patients. Am. J. Cardiol. 55, 65–71 (1985).
Atkinson, J. B. et al. Morphologic changes in long-term saphenous vein bypass grafts. Chest 88, 341–348 (1985).
The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. N. Engl. J. Med. 336, 153–162 (1997).
Une, D., Kulik, A., Voisine, P., Le May, M. & Ruel, M. Correlates of saphenous vein graft hyperplasia and occlusion 1 year after coronary artery bypass grafting: analysis from the CASCADE randomized trial. Circulation 128 (Suppl. 1), S213–S218 (2013).
Harskamp, R. E., Lopes, R. D., Baisden, C. E., de Winter, R. J. & Alexander, J. H. Saphenous vein graft failure after coronary artery bypass surgery: pathophysiology, management, and future directions. Ann. Surg. 257, 824–833 (2013).
Yonetsu, T. et al. Comparison of incidence and time course of neoatherosclerosis between bare metal stents and drug-eluting stents using optical coherence tomography. Am. J. Cardiol. 110, 933–939 (2012).
Otsuka, F. Neoatherosclerosis: overview of histopathologic findings and implications for intravascular imaging assessment. Eur. Heart J. 36, 2147–2159 (2015).
Acknowledgements
CVPath Institute Inc., a private non-profit research organization, provided major support for this work, which was also partially supported by National Institutes of Health grant R01 DK094434-01A1.
Author information
Authors and Affiliations
Contributions
K.Y. and F.D.K. contributed equally to this work. K.Y., F.D.K., F.O., and R.V. substantially contributed to discussion of content. K.Y., F.D.K., F.O., and R.V. wrote the manuscript. F.D.K., F.O., A.V.F., H.R.D., M.J., and R.V. reviewed and edited the manuscript before submission.
Corresponding author
Ethics declarations
Competing interests
F.O. has received speaking honoraria from Abbott Vascular, Bayer, Merck, and Terumo Corporation. A.V.F. receives research support from Boston Scientific and Medtronic, and is a consultant to St. Jude Medical. M.J. is a consultant for Biotronik and Cardionovum, and has received speaking honoraria from Abbott Vascular, Biotronik, Medtronic, and St. Jude Medical. R.V. receives research support from 480 Biomedical, Abbott Vascular, Atrium, Biosensors International, Biotronik, Boston Scientific, Cordis Johnson & Johnson, GSK, Kona, Medtronic, Microport Medical, OrbusNeich Medical, ReCor, SINO Medical Technology, Terumo Corporation, and W. L. Gore; has speaking engagements with Merck; receives honoraria from 480 Biomedical, Abbott Vascular, Biosensors International, Boston Scientific, CeloNova BioSciences, Claret Medical, Cordis Johnson & Johnson, Lutonix Bard, Medtronic, Terumo Corporation, and W. L.Gore; and is a consultant to 480 Biomedical, Abbott Vascular, Medtronic, and W. L. Gore. The other authors declare no competing interests.
PowerPoint slides
Rights and permissions
About this article
Cite this article
Yahagi, K., Kolodgie, F., Otsuka, F. et al. Pathophysiology of native coronary, vein graft, and in-stent atherosclerosis. Nat Rev Cardiol 13, 79–98 (2016). https://doi.org/10.1038/nrcardio.2015.164
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrcardio.2015.164
This article is cited by
-
Risk factors and the CCTA application in patients with vulnerable coronary plaque in type 2 diabetes: a retrospective study
BMC Cardiovascular Disorders (2024)
-
Thylakoid engineered M2 macrophage for sonodynamic effect promoted cell therapy of early atherosclerosis
Nano Research (2024)
-
Transplantation of adipose tissue-derived microvascular fragments promotes therapy of critical limb ischemia
Biomaterials Research (2023)
-
Drug-coated balloon-based versus drug-eluting stent-only revascularization in patients with diabetes and multivessel coronary artery disease
Cardiovascular Diabetology (2023)
-
Evolving concepts of the vulnerable atherosclerotic plaque and the vulnerable patient: implications for patient care and future research
Nature Reviews Cardiology (2023)