Activation of the complement lectin pathway is associated with long-term cardiac dysfunction and incident heart
Baojun Zhong1, Ben King1, Razvan Gheorghita Mares2
1Department of Translational Medicine, Lund University, Jan Waldenströms gata 35, 21428 Malmö, Sweden.
Insights
Persistently high mannose-binding lectin (MBL) levels in acute coronary syndrome (ACS) patients are linked to cardiac dysfunction and increased heart failure risk. This suggests the complement lectin pathway (LP) as a therapeutic target for post-ACS recovery.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Complement System Biology
Background:
- Myocardial injury in acute coronary syndrome (ACS) activates the complement lectin pathway (LP).
- LP inhibition shows promise in experimental models, but its clinical role in ACS is unclear.
- Investigating LP activators mannose-binding lectin (MBL) and ficolin-2 (FCN2) in ACS patients is crucial.
Purpose of the Study:
- To determine the relationship between plasma levels of MBL and FCN2 and cardiac recovery and prognosis in ACS patients.
- To explore the association of MBL and FCN2 with heart failure (HF), stroke, and major adverse cardiovascular events (MACE).
- To examine the link between MBL/FCN2 and inflammatory/fibrotic mediators and left ventricular (LV) remodeling post-ACS.
Main Methods:
- Measured MBL and FCN2 levels at baseline and 6-weeks in 546 ACS patients.
- Assessed prospective associations with HF, stroke, and MACE over 2.2 years using Cox regression.
- Correlated MBL/FCN2 with inflammatory markers and echocardiographic LV parameters.
Main Results:
- Elevated baseline MBL independently predicted incident HF (HR 1.50).
- Persistently high MBL was associated with increased pro-inflammatory/pro-fibrotic mediators, LV dilation, and reduced systolic function at 1-year.
- Ficolin-2 (FCN2) showed no significant association with outcomes.
Conclusions:
- Persistent high plasma MBL levels in ACS patients correlate with cardiac remodeling, dysfunction, and heightened HF risk.
- Findings support the complement LP as a potential therapeutic target to prevent heart failure post-ACS.
- MBL, not FCN2, appears clinically relevant in the context of ACS prognosis.
Background:
Myocardial injury activates the complement lectin pathway (LP) in acute coronary syndrome (ACS) and LP inhibition improved cardiac function in experimental studies, suggesting a direct pathogenic role. The clinical consequences of LP activation are insufficiently defined. We investigated how plasma levels of the LP activators mannose-binding lectin (MBL) and ficolin-2 (FCN2) relate to cardiac recovery and prognosis in ACS patients.
Methods:
MBL and FCN2 were measured at baseline in a cohort of 546 ACS patients and at 6-weeks in 124 patients with available samples. Prospective associations with heart failure (HF), stroke, and major adverse cardiovascular events (MACE) during a median follow-up of 2.2 years were assessed by multivariable Cox regression. Spearman correlation was used to assess relationships between MBL and FCN2 levels, inflammatory and fibrotic mediators in plasma, and echocardiographic parameters of left ventricular (LV) remodelling and dysfunction.
Results:
Baseline MBL was associated with incident HF (HR 1.50, 95% CI 1.04-2.16, p = 0.029), independently of clinical risk factors, revascularization, baseline troponin and renal function. Patients with persistently elevated MBL at baseline and follow-up had increased pro-inflammatory and pro-fibrotic mediators in plasma, dilated LV and reduced LV systolic function at 1-year post-ACS. FCN2 showed no association with the outcomes.
Conclusions:
ACS patients with persistently high plasma MBL levels suffer cardiac remodelling and dysfunction, and have an increased risk for HF. Our findings provide clinical support to experimental data suggesting that the complement LP might be a potential therapeutic target to prevent post-ACS HF.
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