An Atherogenic Diet Exacerbates Vascular Injury in an Experimental Model of Systemic lupus Erythematosus

Abstract

Patients with systemic autoimmune diseases such as systemic lupus erythematosus (SLE) have an increased risk of developing premature atherosclerotic cardiovascular disease (CVD), which is a major contributor to morbidity and mortality in this patient population. Specifically, patients with SLE have evidence of vascular disease including endothelial dysfunction, arterial stiffness, and coronary perfusion abnormalities, all of which predispose them to the development of atherosclerotic lesions. Our laboratory has shown that an established female mouse model of SLE (NZBWF1) develops impaired endothelial dependent relaxation compared to age matched healthy controls (female NZW mice). In the present study, we hypothesized that SLE mice fed an atherogenic diet will have accelerated vascular injury indicative of premature atherosclerotic disease. In order to test this hypothesis, female control (NZW, n=20) and SLE (NZBWF1, n=20) mice were fed normal chow or a high fat diet supplemented with 0.5% cholate (HFD+cholate) for 14 weeks. Body weight and body composition were monitored by Echo MRI biweekly over the course of the study. At the conclusion of the study both carotid arteries and aortas were isolated from control and SLE mice. Carotid rings were suspended in organ chamber baths where endothelium‐dependent and endothelium‐independent relaxation were the concentration responses (10−8 to10−4 M) to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in vessels pre‐contracted with the thromboxane mimetic U46619 (0.4 μg/mL). HFD+cholate did not alter maximal ACh (10−4 M) mediated relaxation (70.1±3.4% vs. 75.2±2.1% p=0.33) in control mice. However, SLE mice fed HFD+cholate had an impaired relaxation response to ACh (10−4 M) as compared to SLE mice fed normal chow (65.6±2.3% vs. 43.6±7.2%, p=0.02). SNP‐mediated relaxation was not different between the mice fed different diets in either control or SLE animals, indicating that the impaired ACh response in SLE mice is endothelial dependent. In order to examine the impact of HFD+cholate on atherosclerotic lesion formation, isolated aortas were subjected to en face staining using Sudan IV. Preliminary data suggest that control mice fed HFD+cholate did not develop atherosclerotic plaques, but SLE fed HFD+cholate showed evidence of plaques in the aortic arch. Taken together, these data suggest that the immune system dysfunction present in SLE may accelerate the progression of diet‐induced atherosclerosis.Support or Funding InformationE.B.T. was supported by an individual NIH National Research Service Award (F32HL137393). This work was supported by Veteran's Administration Merit award (BX002604‐01A2) to M.J.R. and NIH NHLBI awards PO1HL051971, P20GM104357 to UMMC‐Department of Physiology and Biophysics.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.