Complement and contact system activation in acute congestive heart failure patients

Abstract

Recent experimental data indicate a pathogenic role of complement activation in congestive heart failure (CHF). The aim of this study was to evaluate contact and complement systems activation in patients hospitalized for an acute episode of CHF. Forty-two of 80 consecutive patients admitted at our hospital with confirmed diagnosis of acute CHF were enrolled. They underwent blood sampling within 24 h from admission (T0) and at clinical stability (T1). Patients were stratified for ejection fraction (EF) based on echocardiographic test. We measured plasma levels of C3, C4, sC5b-9 and cleaved high molecular weight kininogen (contact activation marker). At T1, C3 levels increased significantly compared to T0 (97 ± 2 versus 104 ± 3% of total pooled plasma, P < 0·01). Classifying patients according to EF, only patients with preserved EF presented a significant increase of C3 from T0 to T1 (99 ± 3 versus 108 ± 4%, P = 0·03). When the sample was stratified according to clinical outcome, C3 (98 ± 3 versus 104 ± 4%, P = 0·03) and sC5b-9 levels (204 ± 10 versus 230 ± 11 ng/ml, P = 0·03) were increased in patients who had positive outcome after hospitalization. CHF patients with preserved EF and positive outcome after hospitalization showed higher levels of sC5b-9 in the T1 period compared with T0 (211 ± 14 versus 243 ± 14 ng/ml, P = 0·04). Our results suggest that the complement system reacts differently if CHF occurs with preserved or reduced EF. This finding is interesting if we consider the difference in epidemiology, pathogenesis and possible therapeutic approaches of these two clinical entities.

Integrated analysis of the proteome and transcriptome in human ischemic cardiomyopathy

“…Similarly, these DEGs were also markedly involved in in ammatory/immune response, response to stress, oxidative stress, and brosis. The exact same terms enriched from DEPs and DEGs furtherly highlighted the key roles of the processes of ECM organization and response to stress, as well as the complement and coagulation cascades signal pathway, in the mechanisms of ICM, which were consistent with previous researches [19][20][21].…”

The role of the complement factor B‒arginase‒polyamine molecular axis in uremia‐induced cardiac remodeling in mice

“…Suffritti et al. also observed in the patients with heart failure that the levels of C4 and C5b9 did not draw back when their cardiac situation became stable; and the C3 levels even manifested confusing elevation at this point . More than C3, de Haan et al.…”

“…Frey et al found that elevated levels of C3c subset, a stable C3-conversion product, even predicted better prognosis in patients with systolic heart failure [22]. Suffritti et al also observed in the patients with heart failure that the levels of C4 and C5b9 did not draw back when their cardiac situation became stable; and the C3 levels even manifested confusing elevation at this point [23]. More than C3, de Haan et al reported that the deficiency of gene encoding C5a receptor failed to significantly improve cardiac fibrosis and collagen degradation in pressure-overload heart failure mice, suggesting the showing that Arg1 (arrow) was the most significantly upregulated gene in BMDMs incubated with CFB.…”

Serum Proteomic Changes in Dogs with Different Stages of Chronic Heart Failure

“…In stage C dogs, C3, a member of the complement system, was up-regulated, whereas other complement proteins (i.e., C4a, C7, and C8) were down-regulated, indicating a pathophysiological involvement of the complement system. The increases in C3 in human patients with CHF is related to chronic immune-inflammatory activation, leading to adverse left ventricular remodeling and aggravation of heart failure [ 31 , 32 ], and poorer outcome [ 31 , 33 ]. The role of complement proteins, as potent therapeutic and prophylactic targets to slow the progression of CHF, should be explored in the future.…”