Angiotensin-Converting Enzyme Inhibition Prevents the Release of Monocytes From Their Splenic Reservoir in Mice With Myocardial Infarction

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Abstract
Rationale:Monocytes recruited to ischemic myocardium originate from a reservoir in the spleen, and the release from their splenic niche relies on angiotensin (Ang) II signaling. Objective:Because monocytes are centrally involved in tissue repair after ischemia, we hypothesized that early angiotensin-converting enzyme (ACE) inhibitor therapy impacts healing after myocardial infarction partly via effects on monocyte traffic. Methods and Results:In a mouse model of permanent coronary ligation, enalapril arrested the release of monocytes from the splenic reservoir and consequently reduced their recruitment into the healing infarct by 45%, as quantified by flow cytometry of digested infarcts. Time-lapse intravital microscopy revealed that enalapril reduces monocyte motility in the spleen. In vitro migration assays and Western blotting showed that this was caused by reduced signaling through the Ang II type 1 receptor. We then studied the long-term consequences of blocked splenic monocyte release in atheroscler...