Cathelicidin Links Visceral Fat Accumulation and Coronary Artery Disease

Abstract

Background: Visceral fat (VF), particularly epicardial adipose tissue (EAT), plays a crucial role in the development of coronary artery disease (CAD). Cathelicidin (LL37) is an antimicrobial peptide involved in innate immunity and has been implicated in inflammatory processes. However, the relationship between VF accumulation, cathelicidin, and atherosclerosis remains unclear.

Methods and Results: Seventy-eight subjects without CAD were enrolled and classified by obesity type: normal-weight (normal; n=20), subcutaneous fat (SF; n=19), and VF (n=39). Plasma LL37 concentrations were compared across groups. LL37 expression in EAT was assessed in 9 patients undergoing open-heart surgery, stratified by CAD status. In animal experiments, angiotensin II-infused wild-type and Apoe^−/−mice fed a Western-type diet were treated with cathelicidin-related antimicrobial peptide (CRAMP) small interfering RNA (siRNA), scrambled siRNA, or vehicle. Atherosclerotic lesions were evaluated by enface Sudan IV staining. Plasma LL37 concentrations were higher in the VF than in the normal-weight and SF groups (median [IQR] 99.11 [91.70–129.86] vs. 58.63 [50.03–70.05] and 69.81 [54.64–87.39] ng/mL, respectively; P<0.001) and were correlated with VF area and EAT volume. LL37 expression in EAT was higher in patients with than without CAD (2.34 [2.06–3.90] % vs. 1.34 [0.81–1.49] %; P=0.034). Treatment with CRAMP siRNA significantly reduced atherosclerotic lesion area in Apoe^−/−mice without affecting blood pressure or lipid profiles.

Conclusions: LL37 is associated with VF accumulation and CAD. However, these findings are exploratory and warrant prospective validation to determine its potential utility as a biomarker.