Thromb Haemost 2016; 115(03): 509-519
DOI: 10.1160/th15-09-0765
Theme Issue Article
Schattauer GmbH

Endothelial erosion of plaques as a substrate for coronary thrombosis

Stephen J. White
1   University of Bristol, School of Clinical Sciences, Bristol, UK
,
Andrew C. Newby
1   University of Bristol, School of Clinical Sciences, Bristol, UK
,
Thomas W. Johnson
1   University of Bristol, School of Clinical Sciences, Bristol, UK
2   Bristol Heart Institute, Bristol, UK
› Author Affiliations
Financial support: This work was supported by British Heart Foundation CH95/001 and the National Health Research Institute (UK) Bristol Biomedical Research Unit in Cardiovascular Medicine.
Further Information

Publication History

Received: 30 September 2015

Accepted after minor revision: 09 January 2015

Publication Date:
20 March 2018 (online)

Summary

Myocardial infarction is a prevalent, life-threatening consequence of athero-thrombosis. Post-mortem histology and intravascular imaging in live patients have shown that approximately one third of myocardial infarctions are caused by a thrombus overlying an intact, non-ruptured atherosclerotic plaque. Histology identifies erosion of luminal endothelial cells from smooth muscle and proteoglycan-rich, thick fibrous cap atheromas as the underlying pathology. Unlike plaque ruptures, endothelial erosions tend to occur on thick-capped atherosclerotic plaques and may or may not be associated with inflammation. Smoking and female gender are strong risk factors for erosion. Multiple mechanisms may contribute to endothelial erosion, including endothelial dysfunction, TLR signalling, leukocyte activation and modification of sub-endothelial matrix by endothelial or smooth muscle cells, which may trigger loss of adhesion to the extracellular matrix or endothelial apoptosis. Diagnosis of endothelial erosion by intravascular imaging, especially high resolution optical coherence tomography, may influence treatment strategies, offering prognostic value and utility as an endpoint in trials of agents designed to preserve an intact coronary endothelium.

 
  • 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.
  • 2 Farb A. et al. Coronary Plaque Erosion Without Rupture Into a Lipid Core: A Frequent Cause of Coronary Thrombosis in Sudden Coronary Death. Circulation 1996; 93: 1354-1363.
  • 3 van der Wal AC. et al. 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; 89: 36-44.
  • 4 Farb A. et al. Coronary plaque erosion without rupture into a lipid core - A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996; 93: 1354-1363.
  • 5 Durand E. et al. In vivo induction of endothelial apoptosis leads to vessel thrombosis and endothelial denudation - A clue to the understanding of the mechanisms of thrombotic plaque erosion. Circulation 2004; 109: 2503-2506.
  • 6 Chiu J, Chien S. Effects of disturbed flow on vascular endothelium: pathophysi-ological basis and clinical perspectives. Physiol Rev 2011; 91: 327-387.
  • 7 Barakat AI. Blood flow and arterial endothelial dysfunction: Mechanisms and implications. C R Phys 2013; 14: 479-496.
  • 8 Chen J. et al. avβ3 Integrins Mediate Flow-Induced NF-κऔ Activation, Proinflammatory Gene Expression, and Early Atherogenic Inflammation. Am J Pathol 2015; 185: 2575-2589.
  • 9 Dimmeler S. et al. Shear stress inhibits apoptosis of human endothelial cells. FEBS Lett 1996; 399: 71-74.
  • 10 Hermann C. et al. Shear Stress Inhibits H2O2-Induced Apoptosis of Human Endothelial Cells by Modulation of the Glutathione Redox Cycle and Nitric Oxide Synthase. Arterioscler Thromb Vasc Biol 1997; 17: 3588-3592.
  • 11 Tricot O. et al. Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques. Circulation 2000; 101: 2450-2453.
  • 12 Kramer MCA. et al. Relationship of Thrombus Healing to Underlying Plaque Morphology in Sudden Coronary Death. J Am Coll Cardiol 2010; 55: 122-132.
  • 13 Arbustini E. et al. Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction. Heart 1999; 82: 269-272.
  • 14 Kolodgie FD. et al. Pathologic assessment of the vulnerable human coronary plaque. Heart 2004; 90: 1385-1391.
  • 15 Virmani R. et al. Pathology of the vulnerable plaque. J Am Coll Cardiol 2006; 47: C13-C18.
  • 16 Kolodgie FD. et al. Differential accumulation of Proteoglycans and hyaluronan in culprit lesions - Insights into plaque erosion. Arterioscler Thromb Vasc Biol 2002; 22: 1642-1648.
  • 17 Tavora F. et al. Sudden coronary death caused by pathologic intimal thickening without atheromatous plaque formation. Cardiovasc Pathol 2011; 20: 51-57.
  • 18 Burke AP. et al. Morphological predictors of arterial remodeling in coronary atherosclerosis. Circulation 2002; 105: 297-303.
  • 19 Sato Y. et al. Proportion of fibrin and platelets differs in thrombi on ruptured and eroded coronary atherosclerotic plaques in humans. Heart 2005; 91: 526-530.
  • 20 Burke AP. et al. Task force #2-what is the pathologic basis for new atherosclerosis imaging techniques?. J Am Coll Cardiol 2003; 41: 1874-1886.
  • 21 Burke AP. et al. Effect of Risk Factors on the Mechanism of Acute Thrombosis and Sudden Coronary Death in Women. Circulation 1998; 97: 2110-2116.
  • 22 Rittersma SZH. et al. Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis - A pathological thrombectomy study in primary percutaneous coronary intervention. Circulation 2005; 111: 1160-1165.
  • 23 Mangold A. et al. Coronary Neutrophil Extracellular Trap Burden and Deoxyri-bonuclease Activity in ST-Elevation Acute Coronary Syndrome Are Predictors of ST-Segment Resolution and Infarct Size. Circ Res 2015; 116: 1182-1192.
  • 24 Lu Q, Rounds S. Focal adhesion kinase and endothelial cell apoptosis. Microvasc Res 2012; 83: 56-63.
  • 25 Ferrante G. et al. High Levels of Systemic Myeloperoxidase Are Associated With Coronary Plaque Erosion in Patients With Acute Coronary Syndromes: A Clini-copathological Study. Circulation 2010; 122: 2505-2513.
  • 26 Yamagishi M. et al. Morphology of vulnerable coronary plaque: insights from follow-up of patients examined by intravascular ultrasound before an acute coronary syndrome. J Am Coll Cardiol 2000; 35: 106-111.
  • 27 Surmely J-F et al.. Coronary plaque composition of culprit/target lesions according to the clinical presentation: a virtual histology intravascular ultrasound analysis. Eur Heart J 2006; 27: 2939-2944.
  • 28 Kubo T. et al. Assessment of Culprit Lesion Morphology in Acute Myocardial Infarction: Ability of Optical Coherence Tomography Compared With Intravas-cular Ultrasound and Coronary Angioscopy. J Am Coll Cardiol 2007; 50: 933-939.
  • 29 Ozaki Y. We should use the OCT-based clinical term „acute coronary syndrome with intact fibrous cap (ACS-IFC)‟ rather than the pathology term „plaque erosion‟. J Am Coll Cardiol 2014; 63: 2745.
  • 30 Ino Y. et al. Difference of culprit lesion morphologies between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome: an optical coherence tomography study. JACC Cardiovasc Interv 2011; 4: 76-82.
  • 31 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 2013; 62: 1748-1758.
  • 32 Prati F. et al. OCT-Based Diagnosis and Management of STEMI Associated With Intact Fibrous Cap. J Am Coll Cardiol 2013; 6: 283-287.
  • 33 Burke AP. et al. Coronary Risk Factors and Plaque Morphology in Men with Coronary Disease Who Died Suddenly. N Engl J Med 1997; 336: 1276-1282.
  • 34 Higuma T. et al. A Combined Optical Coherence Tomography and Intravascu-lar Ultrasound Study on Plaque Rupture, Plaque Erosion, and Calcified Nodule in Patients With ST-Segment Elevation Myocardial Infarction: Incidence, Morphologic Characteristics, and Outcomes After Percutaneous Coronary Intervention. JACC Cardiovasc Interv. 2015 Epub ahead of print.
  • 35 Ozaki Y. et al. Coronary CT angiographic characteristics of culprit lesions in acute coronary syndromes not related to plaque rupture as defined by optical coherence tomography and angioscopy. Eur Heart J 2011; 32: 2814-2823.
  • 36 Tian J. et al. Morphologic characteristics of eroded coronary plaques: a combined angiographic, optical coherence tomography, and intravascular ultrasound study. Int J Cardiol 2014; 176: e137-139.
  • 37 Saia F. et al. Eroded Versus Ruptured Plaques at the Culprit Site of STEMI: In Vivo Pathophysiological Features and Response to Primary PCI. JACC Cardiov-asc Imag 2015; 8: 566-575.
  • 38 Onuma Y. et al. Randomized study to assess the effect of thrombus aspiration on flow area in patients with ST-elevation myocardial infarction: an optical frequency domain imaging study--TROFI trial. Eur Heart J 2013; 34: 1050-1060.
  • 39 Tearney GJ. et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol 2012; 59: 1058-1072.
  • 40 Hu S. et al. Residual Thrombus Pattern in Patients With ST-Segment Elevation Myocardial Infarction Caused by Plaque Erosion Versus Plaque Rupture After Successful FibrinolysisAn Optical Coherence Tomography Study. J Am Coll Cardiol 2014; 63: 1336-1338.
  • 41 Kataoka H. et al. Oxidized LDL modulates Bax/Bcl-2 through the lectinlike Ox-LDL receptor-1 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2001; 21: 955-960.
  • 42 Schwartz RS. et al. Microemboli and Microvascular Obstruction in Acute Coronary Thrombosis and Sudden Coronary DeathRelation to Epicardial Plaque Histopathology. J Am Coll Cardiol 2009; 54: 2167-2173.
  • 43 Orosz Z. et al. Cigarette smoke-induced proinflammatory alterations in the en-dothelial phenotype: role of NAD(P)H oxidase activation. Am J Physiol Heart Circ Physiol 2007; 292: H130-H139.
  • 44 Barbieri SS. et al. Cytokines present in smokers’ serum interact with smoke components to enhance endothelial dysfunction. Cardiovasc Res 2011; 90: 475-483.
  • 45 Edirisinghe I, Rahman I. Cigarette smoke-mediated oxidative stress, shear stress, and endothelial dysfunction: role of VEGFR2. Ann NY Acad Sci 2010; 1203: 66-72.
  • 46 Barua RS, Ambrose JA. Mechanisms of Coronary Thrombosis in Cigarette Smoke Exposure. Arterioscler Thromb Vasc Biol 2013; 33: 1460-1467.
  • 47 Burke AP. et al. Coronary Risk Factors and Plaque Morphology in Men with Coronary Disease Who Died Suddenly. N Engl J Med 1997; 336: 1276-1282.
  • 48 Burke AP. et al. Traditional Risk Factors and the Incidence of Sudden Coronary Death With and Without Coronary Thrombosis in Blacks. Circulation 2002; 105: 419-424.
  • 49 Ferrante G. et al. High levels of systemic myeloperoxidase are associated with coronary plaque erosion in patients with acute coronary syndromes: a clinico-pathological study. Circulation 2010; 122: 2505-2513.
  • 50 van Lammeren GW, den Ruijter HM, Vrijenhoek JE. et al. Time-dependent changes in atherosclerotic plaque composition in patients undergoing carotid surgery. Circulation 2014; 129: 2269-2276.
  • 51 Fujio Y, Walsh K. Akt mediates cytoprotection of endothelial cells by vascular endothelial growth factor in an anchorage-dependent manner. J Biol Chem 1999; 274: 16349-16354.
  • 52 Suhr F, Bloch W. Endothelial cell apoptosis: a new focal adhesion assembly makes the difference. Circ Res 2012; 111: 1488-1490.
  • 53 Burger D, Touyz RM. Cellular biomarkers of endothelial health: microparticles, endothelial progenitor cells, and circulating endothelial cells. J Am Soc Hypertension 2012; 6: 85-99.
  • 54 Woywodt A. et al. Circulating endothelial cells: life, death, detachment and repair of the endothelial cell layer. Nephrol Dial Transplant 2002; 17: 1728-1730.
  • 55 Dignat-George F, Boulanger CM. The many faces of endothelial microparticles. Arterioscler Thromb Vasc Biol 2011; 31: 27-33.
  • 56 Schiro A, Wilkinson FL, Weston R. et al. Endothelial microparticles as conveyors of information in atherosclerotic disease. Atherosclerosis 2014; 234: 295-302.
  • 57 Davies MJ, Woolf N, Rowles PM. et al. Morphology of the endothelium over atherosclerotic plaques in human coronary arteries. Br Heart J 1988; 60: 459-464.
  • 58 Caplan BA, Schwartz CJ. Increased endothelial cell turnover in areas of in vivo Evans Blue uptake in the pig aorta. Atherosclerosis 1973; 17: 401-417.
  • 59 Dimmeler S, Zeiher AM. Endothelial cell apoptosis in angiogenesis and vessel regression. Circ Res 2000; 87: 434-439.
  • 60 Chen XP. et al. Oxidized low density lipoprotein receptor-1 mediates oxidized low density lipoprotein-induced apoptosis in human umbilical vein endothelial cells: role of reactive oxygen species. Vascul Pharmacol 2007; 47: 1-9.
  • 61 Dobler D. et al. Increased dicarbonyl metabolism in endothelial cells in hyper-glycemia induces anoikis and impairs angiogenesis by RGD and GFOGER motif modification. Diabetes 2006; 55: 1961-1969.
  • 62 Quillard T. et al. TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment: implications for superficial erosion. Eur Heart J 2015; 36: 1394-1404.
  • 63 Ballieux BE. et al. Detachment and cytolysis of human endothelial cells by pro-teinase 3. Eur J Immunol 1994; 24: 3211-3215.
  • 64 Macario DK. et al. Inhibition of apoptosis prevents shear-induced detachment of endothelial cells. J Surg Res 2008; 147: 282-289.
  • 65 van Hinsbergh VW, Koolwijk P. Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead. Cardiovasc Res 2008; 78: 203-212.
  • 66 Newby AC. Matrix metalloproteinase inhibition therapy for vascular diseases. Vasc Pharmacol 2012; 56: 232-244.
  • 67 Linder S. The matrix corroded: podosomes and invadopodia in extracellular matrix degradation. Trends Cell Biol 2007; 17: 107-117.
  • 68 Rodella L. et al. Carbon monoxide and biliverdin prevent endothelial cell sloughing in rats with type I diabetes. Free Radic Biol Med 2006; 40: 2198-2205.
  • 69 De Reeder EG, Girard N, Poelmann RE. et al. Hyaluronic acid accumulation and endothelial cell detachment in intimal thickening of the vessel wall. The normal and genetically defective ductus arteriosus. Am J Pathol 1988; 132: 574-585.
  • 70 Langille BL. et al. Adaptations of carotid arteries of young and mature rabbits to reduced carotid blood flow. Am J Physiol 1989; 256: H931-939.
  • 71 Dimmeler S. et al. Fluid shear stress stimulates phosphorylation of Akt in human endothelial cells: involvement in suppression of apoptosis. Circ Res 1998; 83: 334-341.
  • 72 Fry DL. Certain Histological and Chemical Responses of the Vascular Interface to Acutely Induced Mechanical Stress in the Aorta of the Dog. Circ Res 1969; 24: 93-108.
  • 73 Fry DL. Acute Vascular Endothelial Changes Associated with Increased Blood Velocity Gradients. Circ Res 1968; 22: 165-197.
  • 74 Cicha I. et al. Carotid Plaque Vulnerability: A Positive Feedback Between Hae-modynamic and Biochemical Mechanisms. Stroke 2011; 42: 3502-3510.
  • 75 Campbell I. et al. Computational Fluid Dynamics Simulations of Haemody-namics in Plaque Erosion. Cardiovasc Eng Tech 2013; 4: 464-473.
  • 76 He N. et al. Extracellular Matrix can Recover the Downregulation of Adhesion Molecules after Cell Detachment and Enhance Endothelial Cell Engraftment. Sci Rep 2015; 5: 10902.
  • 77 White SJ. et al. Characterization of the differential response of endothelial cells exposed to normal and elevated laminar shear stress. J Cell Physiol 2011; 226: 2841-2848.
  • 78 Chow T. et al. Shear stress-induced von Willebrand factor binding to platelet glycoprotein Ib initiates calcium influx associated with aggregation. Blood 1992; 80: 113-120.
  • 79 Hellums JD. 1993 Whitaker lecture: Biorheology in thrombosis research. Ann Biomed Eng 1994; 22: 445-455.
  • 80 Holme PA. et al. Shear-Induced Platelet Activation and Platelet Microparticle Formation at Blood Flow Conditions as in Arteries With a Severe Stenosis. Ar-terioscler Thromb Vasc Biol 1997; 17: 646-653.
  • 81 Lehoux S. et al. Differential Regulation of Vascular Focal Adhesion Kinase by Steady Stretch and Pulsatility. Circulation 2005; 111: 643-649.
  • 82 Lu D, Kassab GS. Role of shear stress and stretch in vascular mechanobiology. J Royal Soc Interf 2011; 8: 1379-1385.
  • 83 Thodeti CK. et al. TRPV4 Channels Mediate Cyclic Strain-Induced Endothelial Cell Reorientation Through Integrin-to-Integrin Signaling. Circ Res 2009; 104: 1123-1130.
  • 84 Wong DTL. et al. Identification of concomitant ruptured plaque and intracoron-ary thrombus by optical coherence tomography. Lancet 2014; 383: e11.
  • 85 Radu MD, Räber L. Interpretation of optical coherence tomography images. Lancet 2014; 383: 1887.
  • 86 White S. et al. Development of Tissue Characterization Using Optical Coherence Tomography for Defining Coronary Plaque Morphology and the Vascular Responses After Coronary Stent Implantation. Curr Cardiovasc Imag Rep 2014; 7: 1-10.
  • 87 Carrick D. et al. A Randomized Trial of Deferred Stenting Versus Immediate Stenting to Prevent No- or Slow-Reflow in Acute ST-Segment Elevation Myo-cardial Infarction (DEFER-STEMI). J Am Coll Cardiol 2014; 63: 2088-2098.
  • 88 Niccoli G. et al. Plaque rupture and intact fibrous cap assessed by optical coherence tomography portend different outcomes in patients with acute coronary syndrome. Eur Heart J 2015; 36: 1377-1384.
  • 89 Burke AP. et al. Healed plaque ruptures and sudden coronary death - Evidence that subclinical rupture has a role in plaque progression. Circulation 2001; 103: 934-940.
  • 90 Mann J, Davies MJ. Mechanisms of progression in native coronary artery disease: role of healed plaque disruption. Heart 1999; 82: 265-268.
  • 91 Hackshaw A. et al. Long-Term Benefits of 5 Years of Tamoxifen: 10-Year Follow-Up of a Large Randomized Trial in Women at Least 50 Years of Age With Early Breast Cancer. J Clin Oncol 2011; 29: 1657-1663.
  • 92 Grainger DJ. TGF-β and atherosclerosis in man. Cardiovasc Res 2007; 74: 213-222.
  • 93 Niccoli G. et al. Plaque rupture and intact fibrous cap assessed by optical coherence tomography portend different outcomes in patients with acute coronary syndrome. Eur Heart J 2015; 36: 1377-1384.