Abstract 16718: Evidence for the Predictive Role of Alternatively Activated Macrophages for the Outcome of Mechanical Circulatory Support
Background: Ventricular unloading under mechanical circulatory support (MCS) seldom leads to myocardial recovery; the underlying pathophysiological mechanisms for this are largely unknown. Deterioration of left ventricular (LV) function often correlates with elevated fibrosis level (IF). In turn, IF is promoted via the innate immune system, especially by alternatively activated macrophages (M2). We aimed to analyze the effect of alternatively activated macrophages on the level of IF in LV myocardium and on the outcome of MCS therapy.
Methods: With regards to the outcome of patients on MCS, dilatative cardiomyopathy (DCM) patients were separated into two groups. Heart transplantation (HTx) was performed in 13 patients (2 female, age 8- 62 years). Another 7 patients (6 male, age 14-58 years) were weaned from the MCS. We examined the level of IF on Sirius red stained slides with specific software on paraffin embedded myocardium from the site of MCS implantation at the LV apex. The type of chronic inflammation was evaluated by real-time PCR and immunohistochemistry with double immunofluorescence/confocal microscopy, utilizing a specific M2 marker (stabilin-1) and a pan macrophage marker (CD68).
Results: No alternatively activated stabilin-1+ macrophages were detected in patients weaned from MCS, but M2 were present in 7 of 13 HTx patients and 2 of 7 HTx patients had significant CD68+/stabilin-1+ inflammatory infiltrates detected in LV myocardium at the time of HTx.
Real-time PCR shows pro-fibrotic cytokine to stimulate stabilin-1 mRNA levels in monocyte-derived macrophages differentiated in conditions of chronic inflammation (IL-4+IFNgamma). Total IF was elevated in the HTx group (3-24%, mean 12.7%) in comparison with IF level (8%) in all but one weaned patients in the myocardial recovery group (normal <9%).
Conclusion: Our results suggest that not the level of established IF alone, but the phenotype of the inflammatory infiltrate, and specifically the presence of M2, predict myocardial remodeling and thus myocardial recovery under MCS in DCM.
- © 2013 by American Heart Association, Inc.