Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture.

Abstract

BACKGROUND: Rupture of atherosclerotic plaques is probably the most important mechanism underlying the sudden onset of acute coronary syndromes. Macrophages may release lytic enzymes that degrade the fibrous cap and therefore produce rupture of the atherosclerotic plaque. This study was designed to quantify macrophage content in coronary plaque tissue from patients with stable and unstable coronary syndromes. METHODS AND RESULTS: Hematoxylin and eosin and immunostaining with anti-human macrophage monoclonal antibody (PG-M1) were performed. Computerized planimetry was used to analyze 26 atherectomy specimens comprising 524 pieces of tissue from 8 patients with chronic stable angina, 8 patients with unstable angina, and 10 patients with non-Q-wave myocardial infarction. Total plaque area was 417 +/- 87 mm2 x 10(-2) in patients with stable angina, 601 +/- 157 mm2 x 10(-2) in patients with unstable angina, and 499 +/- 87 mm2 x 10(-2) in patients with non-Q-wave myocardial infarction (P = NS). The macrophage-rich area was larger in plaques from patients with unstable angina (61 +/- 18 mm2 x 10(-2)) and non-Q-wave myocardial infarction (87 +/- 32 mm2 x 10(-2)) than in plaques from patients with stable angina (14 +/- 5 mm2 x 10(-2)) (P = .024). The percentage of the total plaque area occupied by macrophages was also larger in patients with unstable angina (13.3 +/- 5.6%) and non-Q-wave myocardial infarction (14.6 +/- 4.6%) than in patients with stable angina (3.14 +/- 1%) (P = .018). Macrophage-rich sclerotic tissue was largest in patients with non-Q-wave myocardial infarction (67 +/- 30 mm2 x 10(-2)) and unstable angina (55 +/- 19 mm2 x 10(-2)) than in patients with stable angina (11.5 +/- 4.1 mm2 x 10(-2)) (P = .046). Macrophage-rich atheromatous gruel was also largest in patients with non-Q-wave myocardial infarction (15 +/- 4 mm2 x 10(-2)) than in patients with unstable angina (3.3 +/- 1.7 mm2 x 10(-2)) or stable angina (2.4 +/- 1.2 mm2 x 10(-2)) (P = .026). CONCLUSIONS: Macrophage-rich areas are more frequently found in patients with unstable angina and non-Q-wave myocardial infarction. This suggests that macrophages are a marker of unstable atherosclerotic plaques and may play a significant role in the pathophysiology of acute coronary syndromes.