Inflammatory Arthritis In K/BxN Mice Is Associated With Abnormal ...

C. Charles-Schoeman1, Ani Shahbazian1, Yuen Yin Lee1 and Srinivasa T. Reddy2, 1Medicine-Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, CA, 2Medicine-Cardiology, UCLA David Geffen School of Medicine, Los Angeles, CA

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Atherosclerosis, Cholesterol and rheumatoid arthritis (RA)

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Session Information

Title: Rheumatoid Arthritis - Animal Models

Session Type: Abstract Submissions (ACR)

Background/Purpose

Patients with rheumatoid arthritis (RA) have significantly increased cardiovascular (CV) morbidity and mortality.  Abnormal function of high density lipoprotein (HDL) has been implicated as a mechanism for this increased CV risk. The current work investigated HDL function in the K/BxN mouse model of RA.

Methods

Male KRN mice were crossed with NOD female mice expressing the MHC class II molecule Ag7 to generate K/BxN mice. 29 mice were assessed for arthritis activity using caliper measurements of hindlimbs and clinical scores 3 times weekly until sacrifice/serum collection at 21 weeks. HDL function was assessed by a previously published cell free assay (A&R 2009; 60: 2870) and paraoxonase 1 (PON1) activity was assessed using both paraoxon and dihydrocumarin as substrates (A&R2013; 65: 2765).  Total and HDL cholesterol (HDL-C) were assessed by standard assays.

Results

Greater arthritis activity measured by higher hind limb scores in K/BxN mice was significantly associated with decreased ability of HDL to inhibit LDL oxidation (higher HDL inflammatory index (HII)); r = 0.5, p=0.01 for correlation of hind limb scores with HII at 21 weeks), and decreased PON1 activity measured using both paraoxon and dihydrocumarin as substrates ( r = -0.6, p=0.0001 and r = -0.7, p