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Intermediate and nonclassical monocytes show heterogeneity in patients with different types of acute coronary
Math P G Leers1, Chantal Stockem1, Dianne Ackermans1
1Department of Clinical Chemistry and Hematology, Zuyderland Medical Center, Heerlen, The Netherlands.
Insights
Monocyte subsets show distinct patterns in acute coronary syndromes (ACS). Differences in classical, intermediate, and nonclassical monocyte expression in ST-elevation myocardial infarction (STEMI) versus non-ST-elevation myocardial infarction (NSTEMI) offer therapeutic targets.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Flow Cytometry
Background:
- Acute coronary syndrome (ACS) encompasses conditions like unstable angina, STEMI, and NSTEMI.
- Monocyte heterogeneity plays a role in inflammatory responses within ACS.
- Understanding monocyte subset differences is crucial for targeted therapies.
Purpose of the Study:
- To investigate monocyte subset heterogeneity in ACS patients.
- To compare monocyte immunophenotypes between STEMI and NSTEMI.
- To identify potential therapeutic targets based on monocyte differences.
Main Methods:
- Blood samples collected during the acute phase of ACS.
- Multiparameter flow cytometry used to analyze monocyte subsets.
- Expression levels of monocyte-associated molecules quantified.
Main Results:
- STEMI patients showed increased leukocyte and monocyte counts across all subtypes.
- Classical monocytes exhibited increased CD11b in NSTEMI but decreased in STEMI.
- CX3CR1 expression significantly decreased on intermediate/nonclassical monocytes in STEMI.
Conclusions:
- Distinct immunophenotypic patterns exist for intermediate and nonclassical monocytes in STEMI vs. NSTEMI.
- These monocyte differences indicate a pro-inflammatory state in NSTEMI.
- Targeting these monocyte subsets may reduce inflammation in myocardial tissue.
Abstract:
This study was performed to gain further insight in the heterogeneity of monocytes in the different categories of acute coronary syndrome (ACS), especially between patients with unstable angina pectoris, ST-elevation myocardial infarction (STEMI), and non-ST-elevation myocardial infarction (NSTEMI). For this purpose, blood samples were collected in the acute phase from patients presenting with an ACS. These samples were examined with multiparameter flow cytometry to identify the different monocyte subsets and to analyze the expression of monocyte-associated molecules. Leukocytes, as well as an absolute number of monocytes, showed a clear and significant increase in patients with STEMI. This increase was seen in all subtypes of monocytes. The classical monocytes (CD14++CD16-) of patients with an NSTEMI had a significantly increased CD11b expression when compared to the control group, while these cells showed a decreased expression pattern in STEMI patients. This increased CD11b-expression was also seen in the intermediate monocytes of NSTEMI, while it was almost completely downregulated on the intermediate monocytes of STEMI. Finally, CX3CR1, which is almost exclusively expressed on intermediate and nonclassical monocytes, showed a significant decrease in expression in patients with STEMI. In conclusion, intermediate and nonclassical monocytes have a different immunophenotypic pattern in patients with STEMI versus NSTEMI. These differences reflect the pro-inflammatory state of the monocytes in NSTEMI and can be used as target molecules for novel therapeutic strategies to diminish the migration of proinflammatory monocytes into the myocardial tissue. © 2017 International Society for Advancement of Cytometry.