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Current Atherosclerosis Reports
Erschienen in: Current Atherosclerosis Reports 4/2014

01.04.2014 | Coronary Heart Disease (JA Farmer, Section Editor)

Pathophysiology of Acute Coronary Syndrome

verfasst von: Carlos G. Santos-Gallego, Belen Picatoste, Juan José Badimón

Erschienen in: Current Atherosclerosis Reports | Ausgabe 4/2014

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Abstract

Despite improvements in interventional and pharmacological therapy for atherosclerotic disease, it is still the leading cause of death in the developed world. Hence, there is a need for further development of more effective therapeutic approaches. This requires better understanding of the molecular mechanisms and pathophysiology of the disease. Recent research in the last decade has changed our view of acute coronary syndrome (ACS): from a mere lipid deposition to an inflammatory disease; from ACS exclusively due to plaque rupture to the novel definitions of plaque erosion or calcified nodule; from the notion of a superimposed thrombus with necessary lethal consequences to the concept of healed plaques and thrombus contributing to plaque progression. In the hope of improving our understanding of ACS, all these recently discovered concepts are reviewed in this article.
Literatur
1.
Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125:e2–e220.PubMedCrossRef
2.•
Folsom AR, Yatsuya H, Nettleton JA, Lutsey PL, Cushman M, Rosamond WD. Community prevalence of ideal cardiovascular health, by the American Heart Association definition, and relationship with cardiovascular disease incidence. J Am Coll Cardiol. 2011;57:1690–6. This is an interesting article highlighting the poor cardiovascular health in the modern world. In this community-based sample of 12,744 patients from the ARIC study, only 0.1 % had ideal cardiovascular health as per the new American Heart Association definition. Those who had the best levels of cardiovascular health nevertheless experienced relatively few events.PubMedCentralPubMedCrossRef
3.
Heidenreich PA, Trogdon JG, Khavjou OA, et al. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011;123:933–44.PubMedCrossRef
4.
Berenson GS, Srinivasan SR, Bao W, Newman 3rd WP, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med. 1998;338:1650–6.PubMedCrossRef
5.
Nemetz PN, Roger VL, Ransom JE, Bailey KR, Edwards WD, Leibson CL. Recent trends in the prevalence of coronary disease: a population-based autopsy study of nonnatural deaths. Arch Intern Med. 2008;168:264–70.PubMedCrossRef
6.
Rajavashisth T, Qiao JH, Tripathi S, et al. Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice. J Clin Invest. 1998;101:2702–10.PubMedCentralPubMedCrossRef
7.
8.
Passlick B, Flieger D, Ziegler-Heitbrock HW. Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood. 1989;74:2527–34.PubMed
9.
Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005;5:953–64.PubMedCrossRef
10.
Ferrante G, Nakano M, Prati F, et al. High levels of systemic myeloperoxidase are associated with coronary plaque erosion in patients with acute coronary syndromes: a clinicopathological study. Circulation. 2010;122:2505–13.PubMedCrossRef
11.
Nahrendorf M, Pittet MJ, Swirski FK. Monocytes: protagonists of infarct inflammation and repair after myocardial infarction. Circulation. 2010;121:2437–45.PubMedCentralPubMedCrossRef
12.
Swirski FK, Libby P, Aikawa E, et al. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest. 2007;117:195–205.PubMedCentralPubMedCrossRef
13.•
Purushothaman M, Krishnan P, Purushothaman KR, et al. Genotype-dependent impairment of hemoglobin clearance increases oxidative and inflammatory response in human diabetic atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32:2769–75. Haptoglobin is responsible for hemoglobin clearance after plaque hemorrhage. The haptoglobin 2–2 genotype causes reduced clearance of hemoglobin, thus creating polarization of the macrophages to M1 response, and increased oxidative, inflammatory, and angiogenic response in human diabetic atherosclerosis.PubMedCrossRef
14.
Purushothaman KR, Purushothaman M, Levy AP, et al. Increased expression of oxidation-specific epitopes and apoptosis are associated with haptoglobin genotype: possible implications for plaque progression in human atherosclerosis. J Am Coll Cardiol. 2012;60:112–9.PubMedCrossRef
15.
Drechsler M, Megens RT, van Zandvoort M, Weber C, Soehnlein O. Hyperlipidemia-triggered neutrophilia promotes early atherosclerosis. Circulation. 2010;122:1837–45.PubMedCrossRef
16.
Ionita MG, van den Borne P, Catanzariti LM, et al. High neutrophil numbers in human carotid atherosclerotic plaques are associated with characteristics of rupture-prone lesions. Arterioscler Thromb Vasc Biol. 2010;30:1842–8.PubMedCrossRef
17.
Sun J, Sukhova GK, Wolters PJ, et al. Mast cells promote atherosclerosis by releasing proinflammatory cytokines. Nat Med. 2007;13:719–24.PubMedCrossRef
18.
Healey JS, Toff WD, Lamas GA, et al. Cardiovascular outcomes with atrial-based pacing compared with ventricular pacing: meta-analysis of randomized trials, using individual patient data. Circulation. 2006;114:11–7.PubMedCrossRef
19.
Vogl T, Tenbrock K, Ludwig S, et al. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med. 2007;13:1042–9.PubMedCrossRef
20.
Viemann D, Barczyk K, Vogl T, et al. MRP8/MRP14 impairs endothelial integrity and induces a caspase-dependent and -independent cell death program. Blood. 2007;109:2453–60.PubMedCrossRef
21.
Huber SA, Sakkinen P, David C, Newell MK, Tracy RP. T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia. Circulation. 2001;103:2610–6.PubMedCrossRef
22.
Zhou X, Nicoletti A, Elhage R, Hansson GK. Transfer of CD4+ T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice. Circulation. 2000;102:2919–22.PubMedCrossRef
23.
Binder CJ, Hartvigsen K, Chang MK, et al. IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis. J Clin Invest. 2004;114:427–37.PubMedCentralPubMedCrossRef
24.
Shimizu K, Shichiri M, Libby P, Lee RT, Mitchell RN. Th2-predominant inflammation and blockade of IFN-γ signaling induce aneurysms in allografted aortas. J Clin Invest. 2004;114:300–8.PubMedCentralPubMedCrossRef
25.
Robertson AK, Rudling M, Zhou X, Gorelik L, Flavell RA, Hansson GK. Disruption of TGF-β signaling in T cells accelerates atherosclerosis. J Clin Invest. 2003;112:1342–50.PubMedCentralPubMedCrossRef
26.
Ludewig B, Freigang S, Jaggi M, et al. Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model. Proc Natl Acad Sci U S A. 2000;97:12752–7.PubMedCentralPubMedCrossRef
27.
28.
Caligiuri G, Nicoletti A, Poirier B, Hansson GK. Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J Clin Invest. 2002;109:745–53.PubMedCentralPubMedCrossRef
29.
Chou MY, Hartvigsen K, Hansen LF, et al. Oxidation-specific epitopes are important targets of innate immunity. J Intern Med. 2008;263:479–88.PubMedCrossRef
30.••
Arbab-Zadeh A, Nakano M, Virmani R, Fuster V. Acute coronary events. Circulation. 2013;125:1147–56. This is a comprehensive review of the pathophysiology of ACS.CrossRef
31.••
Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R. Update on acute coronary syndromes: the pathologists’ view. Eur Heart J. 2013;34:719–28. This is an excellent review, both didactic and detailed, of the recent advances and updated classifications in the pathology of ACS.PubMedCrossRef
32.
Burke AP, Kolodgie FD, Farb A, et al. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation. 2001;103:934–40.PubMedCrossRef
33.
Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000;20:1262–75.PubMedCrossRef
34.
Kubo T, Imanishi T, Takarada S, et al. Assessment of culprit lesion morphology in acute myocardial infarction: ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy. J Am Coll Cardiol. 2007;50:933–9.PubMedCrossRef
35.
Farb A, Burke AP, Tang AL, et al. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation. 1996;93:1354–63.PubMedCrossRef
36.
Sugiyama S, Kugiyama K, Aikawa M, Nakamura S, Ogawa H, Libby P. Hypochlorous acid, a macrophage product, induces endothelial apoptosis and tissue factor expression: involvement of myeloperoxidase-mediated oxidant in plaque erosion and thrombogenesis. Arterioscler Thromb Vasc Biol. 2004;24:1309–14.PubMedCrossRef
37.
Lee JB, Mintz GS, Lisauskas JB, et al. Histopathologic validation of the intravascular ultrasound diagnosis of calcified coronary artery nodules. Am J Cardiol. 2011;108:1547–51.PubMedCrossRef
38.•
Xu Y, Mintz GS, Tam A, et al. Prevalence, distribution, predictors, and outcomes of patients with calcified nodules in native coronary arteries: a 3-vessel intravascular ultrasound analysis from Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT). Circulation. 2012;126:537–45. This was one of the first studies focusing on calcified nodules in the pathogenesis of ACS. Calcified nodules in untreated nonculprit coronary segments in patients with ACS were more prevalent than previously recognized (17 % per artery, 30 % per patient). Interestingly, calcified nodules caused fewer major adverse events during 3 years of follow-up in the PROSPECT trial.PubMedCrossRef
39.•
Jia H, Abtahian F, Aguirre AD, 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;62:1748–58. Plaque erosion is a frequent finding in patients with ACS; patients with plaque erosion are younger, more frequently develop non-ST-elevation MI, and have less lipid core and a thicker fibrous cap. Calcified nodules are the least common cause of ACS, but are commoner in older patients.PubMedCrossRef
40.
Burke AP, Farb A, Malcom GT, Liang Y, Smialek J, Virmani R. Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. Circulation. 1998;97:2110–6.PubMedCrossRef
41.
Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med. 1997;336:1276–82.PubMedCrossRef
42.
Kramer MC, Rittersma SZ, de Winter RJ, et al. Relationship of thrombus healing to underlying plaque morphology in sudden coronary death. J Am Coll Cardiol. 2010;55:122–32.PubMedCrossRef
43.•
Narula J, Nakano M, Virmani R, 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. 2013;61:1041–51. This study seeks to identify histopathological characteristics of vulnerable plaque which can be detected by imaging techniques. Thickness of the fibrous cap less than 55 μm is the best discriminator of plaque vulnerability, followed by necrotic core and macrophage infiltration.PubMedCentralPubMedCrossRef
44.••
Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011;364:226–35. This reports a very ambitious and well designed project prospectively studying which atherosclerosis lesions will develop ACS in the future. It was a true cornerstone in the studies of the pathophysiology of ACS.PubMedCrossRef
45.
Cheruvu PK, Finn AV, Gardner C, et al. Frequency and distribution of thin-cap fibroatheroma and ruptured plaques in human coronary arteries: a pathologic study. J Am Coll Cardiol. 2007;50:940–9.PubMedCrossRef
46.
Rioufol G, Finet G, Ginon I, et al. Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation. 2002;106:804–8.PubMedCrossRef
47.
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.PubMedCrossRef
48.•
Zhao Z, Witzenbichler B, Mintz GS, et al. Dynamic nature of nonculprit coronary artery lesion morphology in STEMI: a serial IVUS analysis from the HORIZONS-AMI trial. JACC Cardiovasc Imaging. 2013;6:86–95. In ST-elevation MI patients, untreated nonculprit lesions did not change during 13-months of follow-up and were accompanied by a decrease in lumen area and an increase in necrotic core.PubMedCrossRef
49.
50.
51.•
Rautou PE, Vion AC, Amabile N, et al. Microparticles, vascular function, and atherothrombosis. Circ Res. 2011;109:593–606. This is a very detailed review of the role of microparticles in atherosclerosis development, progression, and complications by increasing inflammation, stimulating angiogenesis, promoting apoptosis, and stimulating a thrombogenic status in the blood.PubMedCrossRef
52.
Leroyer AS, Isobe H, Leseche G, et al. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J Am Coll Cardiol. 2007;49:772–7.PubMedCrossRef
53.•
Rautou PE, Leroyer AS, Ramkhelawon B, et al. Microparticles from human atherosclerotic plaques promote endothelial ICAM-1-dependent monocyte adhesion and transendothelial migration. Circ Res. 2011;108:335–43. Microparticles isolated from human atherosclerotic plaques transfer ICAM-1 to endothelial cells to recruit inflammatory cells and this suggests that plaque microparticles promote atherosclerosis progression.PubMedCrossRef
54.
Carmeliet P, Mackman N, Moons L, et al. Role of tissue factor in embryonic blood vessel development. Nature. 1996;383:73–5.PubMedCrossRef
55.
Randolph GJ, Luther T, Albrecht S, Magdolen V, Muller WA. Role of tissue factor in adhesion of mononuclear phagocytes to and trafficking through endothelium in vitro. Blood. 1998;92:4167–77.PubMed
56.
Cirillo P, Cali G, Golino P, et al. Tissue factor binding of activated factor VII triggers smooth muscle cell proliferation via extracellular signal-regulated kinase activation. Circulation. 2004;109:2911–6.PubMedCrossRef
57.
Cirillo P, Golino P, Calabro P, et al. C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation. Cardiovasc Res. 2005;68:47–55.PubMedCrossRef
58.
Golino P, Ragni M, Cirillo P, et al. Effects of tissue factor induced by oxygen free radicals on coronary flow during reperfusion. Nat Med. 1996;2:35–40.PubMedCrossRef
Metadaten
Titel
Pathophysiology of Acute Coronary Syndrome
verfasst von
Carlos G. Santos-Gallego
Belen Picatoste
Juan José Badimón
Publikationsdatum
01.04.2014
Verlag
Springer US
Erschienen in
Current Atherosclerosis Reports / Ausgabe 4/2014
Print ISSN: 1523-3804
Elektronische ISSN: 1534-6242
DOI
https://doi.org/10.1007/s11883-014-0401-9

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