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Published on: December 28, 2014
Neutrophil infiltration of culprit lesions in acute coronary syndromes
Takahiko Naruko1, Makiko Ueda, Kazuo Haze
1Department of Cardiology, Osaka City General Hospital, Osaka.
Insights
Neutrophil infiltration is linked to acute coronary events. Specifically, higher numbers of neutrophils expressing neutral endopeptidase (NEP) are found in ruptured plaques, suggesting distinct mechanisms in plaque instability.
Area of Science:
- Cardiovascular Pathology
- Inflammation Research
- Atherosclerosis Studies
Background:
- Neutrophils' role in unstable atherosclerotic lesions is understudied.
- Systemic inflammation is increasingly linked to acute coronary syndromes.
Purpose of the Study:
- To investigate neutrophil infiltration in atherosclerotic plaques.
- To differentiate neutrophil presence in ruptured versus eroded plaques.
- To compare neutrophil levels in stable and unstable angina.
Main Methods:
- Autopsy coronary artery segments from myocardial infarction patients were analyzed.
- Atherectomy specimens from stable and unstable angina patients were examined.
- Immunohistochemistry using antibodies for neutrophils (CD66b, myeloperoxidase) and neutral endopeptidase (NEP, CD10) was performed.
Main Results:
- Neutrophil infiltration was present in all ruptured and eroded plaques.
- NEP-positive neutrophils were significantly higher in ruptured plaques compared to eroded plaques.
- Unstable angina patients showed significantly more neutrophils and NEP-positive cells than stable angina patients.
Conclusions:
- Neutrophil infiltration is actively involved in acute coronary events.
- Elevated NEP-positive neutrophils in ruptured plaques suggest unique pathophysiological pathways.
- These findings highlight neutrophils as potential therapeutic targets in acute coronary syndromes.
Background:
Neutrophils in unstable atherosclerotic lesions have not received much consideration, despite accumulating evidence suggesting a link between systemic inflammation and acute coronary syndromes.
Methods And Results:
Coronary artery segments were obtained at autopsy from 13 patients with acute myocardial infarction (AMI); 8 had a ruptured and 5 an eroded plaque. Patients (n=45) who had died of noncardiovascular diseases served as reference. Atherectomy specimens were obtained from 35 patients with stable angina pectoris (SAP) and from 32 patients with unstable angina pectoris (UAP). Antibodies against CD66b, elastase, myeloperoxidase, and CD11b identified neutrophils; CD10 identified neutral endopeptidase (NEP). CD66b-positive and NEP-positive neutrophils were counted and expressed as a number per square millimeter of tissue. All specimens with plaque rupture or erosion showed distinct neutrophil infiltration; the number did not differ between ruptured and eroded plaques. However, the number of NEP-positive neutrophils was significantly higher (P<0.0001) in ruptured plaques than in eroded plaques. UAP patients showed neutrophils in 14 of 32 culprit lesions; in SAP only 2 of 35 lesions contained neutrophils. The number of neutrophils and NEP-positive cells in patients with UAP was significantly higher (neutrophils, P<0.0005; NEP-positive cells, P<0.005) than in patients with SAP.
Conclusions:
The observations suggest that neutrophil infiltration is actively associated with acute coronary events. The high number of NEP-positive neutrophils in ruptured plaques, compared with eroded plaques, may reflect differences in the underlying pathophysiological mechanisms.
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