LL-37–ApoB-100 Complex Serves as a Biomarker of Coronary Artery Disease

BACKGROUND: ApoB (apolipoprotein B)-containing lipoproteins are causal risk factors for atherosclerotic coronary artery disease (CAD). Since LL-37 (human cathelicidin peptide) binds to ApoB-100 in this pathological context, we investigated whether the circulating LL-37–ApoB-100 complex could serve as a biomarker for CAD. METHODS: We performed surface plasmon resonance and protein-protein docking to demonstrate the direct LL-37–ApoB-100 interaction. We developed a specific polyclonal antibody against the complex and measured its levels in human atherosclerotic plaques and plasma, as well as in Apoe −/− mice. An observational case-control study of 1103 patients undergoing coronary angiography from 2 independent centers assessed the association between LL-37–ApoB-100 and obstructive CAD. RESULTS: We identified that LL-37 directly interacted with multiple distinct binding sites on ApoB-100. Plasma levels of LL-37–ApoB-100 complex were significantly elevated in human patients with atherosclerosis. Consistently, levels of this complex were positively correlated with atherosclerotic plaque area in Apoe −/− mice. In the observational cohort from center 1, plasma LL-37–ApoB-100 levels were also significantly elevated in patients with obstructive CAD and strongly correlated with disease severity (Gensini score; r =0.60, P