Pathophysiology of Acute Coronary Syndrome
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.
KeywordsAcute coronary syndrome Pathophysiology Atherosclerosis Plaque rupture Plaque erosion Calcified nodule Macrophage Platelet Inflammation Innate immune response Adaptative immune response
Compliance with Ethics Guidelines
Conflict of Interest
Carlos G. Santos-Gallego, Belen Picatoste, and Juan José Badimón declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 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.PubMedCentralPubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.PubMedCentralPubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar