Abstract 10844: Pitavastatin Reduces Inflammation in Atherosclerotic Plaques in Hyperlipidemic Mice with Chronic Renal Disease
Background: Chronic renal disease (CRD) accelerates atherosclerosis and cardiovascular calcification. Statins lower LDL-cholesterol levels in patients with CRD, however, the benefits of statins on cardiovascular disease in CRD remain unclear. We therefore investigated the effects of pitavastatin treatment on arterial inflammation and calcification in atherogenic mice with CRD induced by 5/6 nephrectomy.
Methods: High-cholesterol-fed apolipoprotein E-deficient (apoE-/-) mice at 21 weeks of age were randomized to control mice (n=10) and CRD mice treated or untreated with pitavastatin (n=20 each). Pitavastatin (0.01% wt/wt) was administered as a food admixture for 10 weeks after surgery. Development of luminal stenosis in innominate artery was monitored by ultrasonography before nephrectomy and at the end of the study. Tissue harvesting for ex vivo near infrared (NIR) molecular imaging and histological analyses was performed at 32 weeks.
Results: CRD mice had significantly higher levels of plasma phosphate (P<0.01), creatinine (P<0.05), cystatin C (P<0.01), and urea (P<0.01) than control mice. As documented in previous mouse studies, pitavastatin treatment did not lower total cholesterol levels in mice. Ultrasound imaging showed progression of luminal stenosis with age and after nephrectomy and significant reduction of stenosis in pitavastatin-treated CRD mice (P<0.01). Histological measurements of plaque size and luminal stenosis corroborated in vivo imaging results. Molecular imaging (AminoSPARK 750) and correlated histological analysis for Mac3 showed reduction in macrophage accumulation (P<0.01) in pitavastatin-treated CRD mice. An induction in plasma levels of osteopontin (OPN), a pro-inflammatory protein, and an increase of arterial OPN expression examined by immunohistochemistry was decreased by pitavastatin treatment (P<0.01). However, pitavastatin did not affect arterial calcification as determined by NIR molecular imaging for calcium content (OsteoSense 680) and histological analysis (von Kossa).
Conclusions: This study provides in vivo evidence that pitavastatin reduces stenosis and inflammation within atherosclerotic lesions in CRD through the mechanisms independent of its lipid lowering effects.
- © 2012 by American Heart Association, Inc.