IntroductionThe purpose of this study was to evaluate the effects of L-4F, an apolipoprotein A-1 mimetic peptide, alone or with pravastatin, in apoE-/-Fas-/-C57BL/6 mice that spontaneously develop immunoglobulin G (IgG) autoantibodies, glomerulonephritis, osteopenia, and atherosclerotic lesions on a normal chow diet.MethodsFemale mice, starting at eight to nine weeks of age, were treated for 27 weeks with 1) pravastatin, 2) L-4F, 3) L-4F plus pravastatin, or 4) vehicle control, followed by disease phenotype assessment.ResultsIn preliminary studies, dysfunctional, proinflammatory high-density lipoproteins (piHDL) were decreased six hours after a single L-4F, but not scrambled L-4F, injection in eight- to nine-week old mice. After 35 weeks, L-4F-treated mice, in the absence/presence of pravastatin, had significantly smaller lymph nodes and glomerular tufts (PL, LP < 0.05), lower serum levels of IgG antibodies to double stranded DNA (dsDNA) (PL < 0.05) and oxidized phospholipids (oxPLs) (PL, LP < 0.005), and elevated total and vertebral bone mineral density (PL, LP < 0.01) compared to vehicle controls. Although all treatment groups presented larger aortic root lesions compared to vehicle controls, enlarged atheromas in combination treatment mice had significantly less infiltrated CD68+ macrophages (PLP < 0.01), significantly increased mean α-actin stained area (PLP < 0.05), and significantly lower levels of circulating markers for atherosclerosis progression, CCL19 (PL, LP < 0.0005) and VCAM-1 (PL < 0.0002).ConclusionsL-4F treatment, alone or with pravastatin, significantly reduced IgG anti-dsDNA and IgG anti-oxPLs, proteinuria, glomerulonephritis, and osteopenia in a murine lupus model of accelerated atherosclerosis. Despite enlarged aortic lesions, increased smooth muscle content, decreased macrophage infiltration, and decreased pro-atherogenic chemokines in L-4F plus pravastatin treated mice suggest protective mechanisms not only on lupus-like disease, but also on potential plaque remodeling in a murine model of systemic lupus erythematosus (SLE) and accelerated atherosclerosis.

OBJECTIVE To evaluate and report measurements of the radiographic cardiac silhouette of healthy juvenile and adult ospreys (Pandion haliaetus). ANIMALS 54 ospreys (22 adults, 19 juveniles, and 13 birds of undetermined age) without clinical signs of cardiac disease and with adequate ventrodorsal radiographic images for cardiac silhouette assessment. PROCEDURES Radiographs of ospreys were assessed to determine cardiac width at the widest point as well as sternal width and thoracic width at the same level. Two-way mixed-effects models were used to evaluate interrater reliability for mean rating. Multivariable linear regression analysis was used to create predictive models of cardiac width and to establish a theoretical reference range for healthy ospreys. RESULTS Cardiac width of healthy ospreys was approximately 90% to 92% of sternal width and 67% to 69% of thoracic width. Both sternal width and thoracic width were significant predictors of cardiac width in independent predictive models as well as in a combined model after controlling for age. Thirty-four of 41 (83%) measured cardiac widths were within the theoretical reference range. CONCLUSIONS AND CLINICAL RELEVANCE Ospreys are sentinels used in monitoring environmental health. Environmental factors may have an impact on the cardiac health of ospreys, but reference values for healthy ospreys have not been established for use in assessing cardiomegaly in this species. The radiographic ratios and predictive model obtained in this study may be useful for objective evaluation of cardiomegaly in ospreys.