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Atherosclerosis, Introduction and Pathophysiology

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Pathophysiology and Pharmacotherapy of Cardiovascular Disease

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Abstract

Patients with acute coronary syndrome classically present with unstable angina, acute myocardial infarction, or sudden coronary death. In approximately 50–60 % of sudden coronary death cases, the culprit lesion exhibits an acute coronary thrombus, whereas the remainder of these cases have stable coronary plaques with greater than 75 % cross-sectional area luminal narrowing with or without chronic total occlusion or healed myocardial infarction. There are three main causes of coronary thrombosis: plaque rupture, erosion, and calcified nodule originally described from observations made at autopsy but now confirmed by optical coherence tomography. The most common cause of coronary thrombus is plaque rupture, which is characterized by a large necrotic core and a disrupted thin fibrous cap rich in macrophages that allows blood to come in contact with the highly thrombogenic necrotic core inducing luminal thrombosis. A few decades ago, it was proposed that matrix metalloproteinases liberated from macrophages were the main mechanism of fibrous cap disruption in coronary plaque rupture. On the other hand, in plaque erosion the platelet-rich thrombus is in direct contact with the intima, and the latter is rich in smooth muscle cells and proteoglycan-collagen matrix with an absence of endothelial lining. The underlying plaque in erosions consists of either pathological intimal thickening or thick fibrous cap fibroatheroma, and the frequency of these underlying lesions is similar. Calcified nodule is the least frequent cause of coronary thrombosis, which occurs in highly calcified arteries. The highly calcified arteries are composed of calcified sheets which likely break into multiple small calcified nodules that are surrounded by fibrin with a luminal thrombus. The eruptive calcified nodules are usually eccentric, protruding into the lumen, and there is an absence of endothelium and collagen above the nodules, and there is an associated platelet-rich luminal thrombus which is typically nonocclusive. This chapter focuses on plaque progression and includes the three responsible entities of thrombosis as we have learnt from studies carried out in sudden coronary death victims.

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Authors and Affiliations

  1. CVPath Institute, Inc., 19 Firstfield Road, Gaithersburg, MD, 20878, USA

    Kazuyuki Yahagi MD, Harry R. Davis PhD, Michael Joner MD & Renu Virmani MD

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  2. Harry R. Davis PhD
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  4. Renu Virmani MD
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Correspondence to Renu Virmani MD .

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  1. Center for Drug Evaluation and Research Division of Cardiovascular and Renal Products, US Food and Drug Administration, Silver Spring, Maryland, USA

    Gowraganahalli Jagadeesh

  2. Pharmacology Unit, AIMST University, Bedong, Malaysia

    Pitchai Balakumar

  3. Center for Drug Evaluation and Research Division of Cardiovascular and Renal Products, US Food and Drug Administration, Silver Spring, Maryland, USA

    Khin Maung-U

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Yahagi, K., Davis, H.R., Joner, M., Virmani, R. (2015). Atherosclerosis, Introduction and Pathophysiology. In: Jagadeesh, G., Balakumar, P., Maung-U, K. (eds) Pathophysiology and Pharmacotherapy of Cardiovascular Disease. Adis, Cham. https://doi.org/10.1007/978-3-319-15961-4_25

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