Abstract 13813: Prior β-Blocker Treatment Dampens Immune Cell Responses Following Myocardial Infarction
Following myocardial infarction (MI), immune cell infiltration initiates and regulates cardiac remodeling and repair. Our previous work has shown the importance of β2-adrenergic receptors (β2AR) in modulating immune cell infiltration to the heart following injury through the regulation of chemokine receptor expression and splenic retention of bone marrow (BM)-derived leukocyte populations. Pharmacological inhibition of βAR is a common strategy for the treatment of many cardiovascular etiologies, however the impact of β-blocker therapy on immune cell responses following acute cardiac injury is unknown. We hypothesized that prior treatment with β-blockers with distinct isoform selectivity would differentially decrease leukocyte infiltration to the heart following MI. Mice were administered either vehicle, a β1AR-selective (Metoprolol; Met), a β2AR-selective (ICI 118,551; ICI) or a βAR non-selective (Carvedilol; Carv) antagonist for two weeks via minipump. Analysis of mice treated with ICI or Carv showed decreased BM expression of CCR2 and CXCR4, as well as elevated levels of leukocyte populations within the spleen. While these effects were not observed in mice infused with a β1AR-selective dose of Met, a higher concentration of Met (equivalent to moderate doses used in humans) also decreased CCR2 and CXCR4 expression in BM and increased splenic leukocyte retention. To determine the impact of β2AR-selective versus non-selective blockade on immune cell responses following acute cardiac injury, mice from each treatment group underwent sham or MI surgery. In addition to decreased CCR2 and CXCR4 expression in the BM, mice administered ICI, Carv and the non-selective dose of Met had impaired recruitment of leukocyte populations to the heart following MI. Toward clinically relevant ends, we assessed CCR2 and CXCR4 expression in leukocytes isolated from blood samples of healthy and heart failure patients and found that levels of each were decreased in patients having taken β-blockers. In all, these results demonstrate that prior β-blocker treatment negatively regulates immune cell responsiveness to acute cardiac injury.
Author Disclosures: L.A. Grisanti: None. E. Gao: None. W.J. Koch: None. D.G. Tilley: None.
- © 2016 by American Heart Association, Inc.