Introduction: Phosphorylcholine (PC) is a pro-inflammatory epitope in oxidized phospholipids in atherosclerotic lesions. Low levels of natural antibodies against PC are associated with increased risk of cardiovascular events, but their effects on atherosclerotic lesions and vascular function are unknown.

Purpose: We studied the effects of short-term treatment with a mouse-human chimeric antibody against PC (mouse Fc and human Fab fragment, designated X19-mu) on inflammation in atherosclerotic lesions and coronary vascular function in mice.

Methods: Atherosclerotic mice deficient of low density lipoprotein receptor and expressing only apolipoprotein B100 (LDLR-/-ApoB100) were randomized to weekly intraperitoneal injections of either X19-mu (10 mg/kg) or saline (placebo) for 6 weeks (n=16-18/group) at the age of 5 months after 3 months on high-fat diet (baseline). After treatments, vessel wall inflammation was measured by uptake of positron emission tomography (PET) tracer 18F-fluorodeoxyglucose (18F-FDG, autoradiography) and immunohistochemical staining of macrophages (Mac-3 antibody) in aortic tissue sections. Coronary flow reserve (CFR) was measured as left coronary artery flow velocity during adenosine-induced maximal vasodilatation and at rest by Doppler ultrasound at baseline and after treatments.

Results: Treatment with X19-mu was well tolerated and had no effect on cholesterol levels. Plaque burden in the aortic root was comparable in placebo and X19-mu groups (intima-to-media ratio 2.6±0.8 vs. 2.5±1.3, p=0.80). Compared with placebo, treatment with X19-mu reduced areal percentage of macrophages (12±3 % vs. 8±2 %, p=0.001) and uptake of 18F-FDG (plaque-to-normal vessel wall ratio 1.8±0.2 vs. 1.6±0.2, p=0.026) in atherosclerotic plaques. Compared with baseline, CFR was 24 % (p=0.005) lower after 6 weeks in placebo, but it was comparable (+7 %, p=0.46) after 6 weeks treatment with X19-mu.

Conclusions: Short-term treatment with X19-mu attenuated inflammation in atherosclerotic lesions and preserved vascular function in mice. Non-invasive imaging techniques may be useful to monitor potential therapeutic effects of PC antibody therapy in man.