Impact of Heterogeneity of Human Peripheral Blood Monocyte Subsets on Myocardial Salvage in Patients With Primary Acute Myocardial Infarction

Abstract

We examined whether distinct monocyte subsets contribute in specific ways to myocardial salvage in patients with acute myocardial infarction (AMI). Recent studies have shown that monocytes in human peripheral blood are heterogeneous. 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. 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. 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.