Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction.

OBJECTIVES: We examined whether distinct monocyte subsets contribute in specific ways to myocardial salvage in patients with acute myocardial infarction (AMI). BACKGROUND: Recent studies have shown that monocytes in human peripheral blood are heterogeneous. METHODS: We studied 36 patients with primary AMI. Peripheral blood sampling was performed 1, 2, 3, 4, 5, 8, and 12 days after AMI onset. Two monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) were measured by flow cytometry. The extent of myocardial salvage 7 days after AMI was evaluated by cardiovascular magnetic resonance imaging as the difference between myocardium at risk (T2-weighted hyperintense lesion) and myocardial necrosis (delayed gadolinium enhancement). Cardiovascular magnetic resonance imaging was also performed 6 months after AMI. RESULTS: Circulating CD14(+)CD16(-) and CD14(+)CD16(+) monocytes increased in AMI patients, peaking on days 3 and 5 after onset, respectively. Importantly, the peak levels of CD14(+)CD16(-) monocytes, but not those of CD14(+)CD16(+) monocytes, were significantly negatively associated with the extent of myocardial salvage. We also found that the peak levels of CD14(+)CD16(-) monocytes, but not those of CD14(+)CD16(+) monocytes, were negatively correlated with recovery of left ventricular ejection fraction 6 months after infarction. CONCLUSIONS: The peak levels of CD14(+)CD16(-) monocytes affect both the extent of myocardial salvage and the recovery of left ventricular function after AMI, indicating that the manipulation of monocyte heterogeneity could be a novel therapeutic target for salvaging ischemic damage.