Abstract:
Aim: Immune mechanisms and inflammation contribute to the pathophysiology of heart failure (HF) in different ways. As the center of immune response, dendritic cells (DCs) play an important role in LV remodeling after myocardial ischemia and myocarditis, however, the role of dendritic cells in non-ischemic HF with volume overload has not be addressed, so far. Here, we investigated the number and phenotype of circulating DC precursors in a patient collective undergoing percutaneous mitral valve repair (PMVR) of mitral regurgitation to uncover the potential crosstalk of volume overload HF with immune regulation. Methods: Using flow cytometry, we determined the numbers of circulating myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and their surface expression of co-stimulatory molecules CD40, CD86, HLA-DR, as well as adhesion molecule CD11a in healthy control subjects (n=11) and MR patients at the time of PMVR (n=125) and at a median follow-up (n=80) of 5.8 (4 to 10) months. Levels of plasma inflammatory cytokines and change in left ventricular end-diastolic diameter (LVEDD) were assessed, and a 6-minute walk test was carried out prior to PMVR and during follow-up. Results: Compared to controls (mDC 10.38/µl and pDC 5.44/µl, respectively), patients with MR had significantly decreased numbers of circulating mDC precursors (6.87/µl, P<0.01), whereas there was no significant difference regarding pDC precursors (4.86/µl). While a significant up-regulation of mDC surface expression of CD11a (mean fluorescence intensity (MFI) 160, P<0.05) was detected compared to healthy controls (MFI: 130), no significant differences for CD40, CD86 and HLA-DR were found. During follow-up, PMVR treatment restored reduction of circulating mDC precursors (8.93/µl, P<0.001). Furthermore, we observed an increase in circulating pDC precursors (6.56/µl, P<0.01). Simultaneously, surface expression of CD11a on circulating mDC and pDC significantly decreased after PMVR. The increased numbers of circulating DC precursors after PMVR was paralleled by a reduction of CRP, IL6 levels, decreased LVEDD and an improvement of 6-minute walk test distance. Interestingly, the change in mDC levels showed a positive correlation with 6-minute walk test distance and an inverse correlation with inflammatory markers CRP and IL-6. Conclusions: Our findings suggest that the change of circulating DC precursors may be involved in the pathophysiology of MR relevant HF.
