Anti-phosphorylcholine therapy restricts left ventricular remodeling after myocardial ischemia-reperfusion injury in hypercholesterolemic APOE*3-Leiden mice

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Purpose: Antibodies against phosphorylcholine (αPC) are known to have anti-inflammatory properties and ameliorate atherosclerosis development. Low IgM αPC levels are associated with development of cardiovascular diseases. Therefore, we investigated the effect of a monoclonal antibody against phosphorylcholine (PC-mAb) on left ventricular (LV) function and remodeling 3 weeks after myocardial ischemia-reperfusion (MI-R) injury in hypercholesterolemic APOE*3-Leiden mice. Methods: We investigated the effects of PC-mAb application (10mg/kg every 3rd day) on LV remodeling after MI-R injury in hypercholesterolemic APOE*3-Leiden mice compared with a vehicle-control and sham-operated group. After 45 minutes of ischemia by occlusion of the left anterior descending coronary artery permanent reperfusion was induced. LV function was assessed 2 and 20 days after MI-R using 7T magnetic resonance imaging (MRI) including delayed-enhancement MRI using gadolinium (Gd)-DPTA contrast agent. Histological analysis of infarct size (IS) and LV wall thickness were performed by Sirius Red staining 21 days post-reperfusion. Results: After 20 days, PC-mAb reduced LV end-diastolic volume (EDV; 33.7±1.4μl vs. 44.3±2.3μl, P<0.001) and end-systolic volume (ESV; 15.5±0.9μl vs. 26.0±2.2μl, P<0.001) compared with vehicle. LV volumes in the PC-mAb and sham operated group (EDV 30.3±1.2μl, P=0.59, and ESV 11.1±1.0μl, P=0.19 respectively) were not significantly different. LV ejection fraction (EF) decrease was observed in both PC-mAb (54.1±1.8%, P=0.028) and vehicle (41.8±2.9%, P<0.001) groups compared with sham mice (63.8±2.1%) but PC-mAb showed a better preserved EF compared with vehicle (P=0.002). After 2 days, delayed-enhancement MRI showed no difference in IS between the PC-mAb and vehicle groups (28.3±1.4% vs. 30.4±2.0%, P=0.40). However, IS 21 days after MI-R was reduced in the PC-mAb compared with the vehicle group (13.7±1.4% vs. 19.0±1.8%, P=0.048) accompanied with a trend towards increased LV wall thickness of the border zone (1.11±0.07mm vs. 0.99±0.10mm, P=0.066) and infarcted area (0.79±0.09mm vs. 0.67±0.12mm, P=0.12). Conclusion: PC-mAb treatment restricts infarct expansion, left ventricular remodeling, and preserves cardiac function after myocardial ischemia-reperfusion injury in hypercholesterolemic APOE*3-Leiden mice.