Abstract 1951: Circulating Dendritic Cells May Play an Important Role in Pathophysiology in Heart Failure in Humans
Dendritic cells (DCs) are the most potent antigen-presenting cells and play a central role in initiating the primary immune response. Although increasing evidence supports immune-mediated inflammation plays an important role in the pathophysiology of heart failure, little is known regarding the source and mechanism that trigger immune responses. The present study examined whether circulating DCs have any role in the pathophysiology in heart failure in humans.
Methods and Results: With multi-color flow-cytometry we determined the numbers of circulating myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in decompensated heart failure patients with NYHA class III or IV on admission (n=27) and the age-matched control subjects (n=21). DC activation markers such as CD40 and CCR7 were also measured. On admission, circulating mDC and pDC counts were significantly lower in decompensated heart failure patients compared to control subjects (12417 ± 2849 versus 5394 ± 3547 and 3321 ± 1491 versus 1800 ± 1474/ml, respectively, p<0.01). Circulating DCs were activated in the decompensated heart failure patients compared to control subjects (CD40; 1.6 ± 1.8 versus 8.5 ± 9.2, CCR7; 3.5 ± 4.1 versus 13.5 ± 10.0, respectively, p<0.05). Heart failure treatment significantly restored the reduction and the activation of circulating DCs (p<0.05). The increases of circulating DCs numbers after treatment were correlated with the decreases in B-type natriuretic peptide (BNP) and troponin-T (r=0.64, p<0.01 and r=0.46, respectively, p<0.05) and with the increase in left ventricular ejection fraction (LVEF) (r=0.73, p<0.01). Furthermore, we found that patients with smaller circulating DCs numbers (less than 10000/ml) after heart failure treatment had poor prognosis compaired with those who had greater DCs numbers (more than 10000/ml) during the 6-month follow-up (p<0.01). Thus, we found that changes of circulating DCs numbers were well correlated with cardiac injury and function, and that poor recovery of the circulating DCs number after treatment predicted recurrence of decompensated heart failure.
Conclusion: These findings suggest that circulating DCs may play an important role in pathophysiology in heart failure in humans.