A 60-year-old man is brought to the emergency department due to acute onset of chest pain. Medical history is significant for smoking 1 pack per day for the past 30 years, diabetes mellitus type 2, and hypertension. An ECG shows ST-segment elevation on V1-V4 leads. Cardiac catheterization is performed and shows 80% occlusion of the left anterior descending artery. The first step in the pathogenesis of this patient’s condition most likely involves which of the following cell types?
A. Macrophages
B. Smooth muscle cells
C. Platelets
D. Endothelial cells
E. Monocytes
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The correct answer to today’s USMLE® Step 1 Question is…
D. Endothelial cells
This patient is likely having an acute myocardial infarction complicated by atherosclerosis. Before we go into the full answer explanation, let’s review the incorrect answers.
Incorrect answer explanations
The incorrect answers to today’s USMLE® Step 1 Question are…
A. Macrophages
Incorrect: Macrophages participate in the pathogenesis of atherosclerosis but do not initiate it.
B. Smooth muscle cells
Incorrect: Smooth muscle cells participate in the pathogenesis of atherosclerosis but do not initiate it.
C. Platelets
Incorrect: Platelets participate in the pathogenesis of atherosclerosis but do not initiate it.
E. Monocytes
Incorrect: Monocytes participate in the pathogenesis of atherosclerosis but do not initiate it.
Correct answer explanation
This patient’s presentation and ECG findings are consistent with acute myocardial infarction, which, given the patient’s risk factors, is most likely due to atherosclerosis of the coronary arteries.
Atherosclerosis is a pathologic process that affects arteries throughout the body, including the aorta, coronary, cerebral, and peripheral arteries. Atherosclerosis is the hardening of any artery (but usually medium-large arteries), which is caused by the buildup of plaques (termed “atheromas”). Atherosclerosis can begin as early as childhood with the development of fatty streaks and advances with aging. The current hypothesis of the pathogenesis is the response-to-injury model, which is as follows:
- Endothelial cell injury due to hypertension, smoking, hyperlipidemia, homocysteine, or diabetes is the first step in pathogenesis. Injury to endothelial cells results in endothelial dysfunction, increased membrane permeability, leukocyte adhesion, and thrombosis.
- Lipoproteins, mainly oxidized LDL and cholesterol crystals, aggregate in the blood vessel wall.
- Platelets (choice C) adhere to exposed collagen and are activated.
- Monocytes (choice E) adhere to the endothelium, migrate into the intima, and differentiate into macrophages. Macrophages (choice A) engulf LDL, becoming foam cells (macrophages ingest LDL and become laden with lipids, which gives them a foamy appearance). The macrophages with engulfed lipids eventually undergo apoptosis (fatty streak) and release toxic oxidized LDL and inflammatory cytokines.
- At the same time, growth factors and inflammatory cytokines released from the activated platelets, macrophages, and endothelial cells then recruit smooth muscle cells (choice B).
- The growing smooth muscle secretes collagen, proteoglycans, and elastin fibrous cells, which all help form a wall around the fatty streak. The lipid core center surrounded by a fibrous cap is termed “fibrous plaque.”
- When the formed fibrous plaques rupture due to shearing forces of blood flow, thrombogenic material (e.g., collagen) is exposed, which allows platelets to adhere to it. This buildup of platelets eventually occludes the artery and results in myocardial infarction, as seen in this patient.
Major takeaways
Atherosclerosis is a pathologic process that mainly affects medium to large arteries. The pathogenesis begins with an endothelial injury, followed by chronic inflammation and the formation of fibrous plaques that obstruct the lumen.
References
Kumar, V., Abbas, A. K., Aster, J. C., Perkins, J. A., & Robbins, S. L. (2018). Robbins Basic Pathology (10th ed.). Philadelphia, PA: Elsevier.
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