Abstract
Brown bears (Ursus arctos) hibernate for 5–6 months during winter, but despite kidney insufficiency, dyslipidemia and inactivity they do not seem to develop atherosclerosis or cardiovascular disease (CVD). IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) are associated with less atherosclerosis, CVD and mortality in uremia in humans and have anti-inflammatory and other potentially protective properties. PC but not MDA is exposed on different types of microorganisms. We determine anti-PC and anti-MDA in brown bears in summer and winter. Paired serum samples from 12 free ranging Swedish brown bears were collected during hibernation in winter and during active state in summer and analyzed for IgM, IgG, IgG1/2 and IgA anti-PC and anti-MDA by enzyme linked immunosorbent assay (ELISA). When determined as arbitrary units (median set at 100 for summer samples), significantly raised levels were observed in winter for anti-PC subclasses and isotypes, and for IgA anti-PC the difference was striking; 100 IQR (85.9–107.9) vs 782.3, IQR (422.8–1586.0; p < 0.001). In contrast, subclasses and isotypes of anti-MDA were significantly lower in winter except IgA anti-MDA, which was not detectable. Anti-PCs are significantly raised during hibernation in brown bears; especially IgA anti-PC was strikingly high. In contrast, anti-MDA titers was decreased during hibernation. Our observation may represent natural immunization with microorganisms during a vulnerable period and could have therapeutic implications for prevention of atherosclerosis.
Highlights
Estimates comparable with smoking and hypertension[6]
We have measured the unit values for each sample according to the equation: Arbitrary unit value = Average optical density (OD) at 450 nm − Average blank OD at 450 nm
When determined as arbitrary units (AU) with median set at 100 at summer marked and significant differences were observed between summer and winter for IgM anti-MDA; (100 IQR (76.1–144.6) vs 75.7, IQR (70.0–89.9; p < 0.01)), IgG anti-MDA; 100
Summary
Estimates comparable with smoking and hypertension[6]. These and similar findings have largely been confirmed and extended to mortality in CKD and systemic rheumatic disease including S LE6,13,15–25. The role of IgG anti-MDA is less clear and since IgG2 anti-MDA is associated with increased mortality in uremia it may instead be n egative[28]. IgG1 and IgA anti-PC has similar properties as IgM anti-PC, associated with protection in atherosclerosis progress[29]. We have reported that IgM and IgG1 anti-PC is associated with longevity in C KD30. Given the protection against arteriosclerosis in a dyslipidemic and uremic milieu we analyzed anti-PC and anti-MDA in paired summer (active state) and winter (hibernation) bear samples and report that anti-PC, especially IgA and IgG1 are strikingly high in hibernating bears in contrast to anti-MDA
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