Atherosclerosis is driven partly by inflammation, mediated mainly by pro-inflammatory mediators/cytokines. Previous studies have revealed the role of HMGB1, a prototypic DAMP (damage-associated molecular pattern) molecule, in atherogenesis. Recently, we have found that there is a spontaneous production of a neutralizing anti-HMGB1 IgM antibody in the Apoe−/− mouse model of atherosclerosis and healthy humans. In the present study, we have determined whether raising the anti-HMGB1 IgM, via immunization targeting HMW4 (a dominant epitope of HMGB1), reduces atherosclerosis. We first showed that the immunization of 8-week-old Apoe−/− C57BL/6 mice increased the HMW4-specific B-1 cells (which produce anti-HMW4 IgM), identified by HMW4-tetramer staining/flow cytometry. Next, we assessed the anti-atherogenic efficacy of the immunization. To the end, 8-week-old Apoe−/− mice were divided into 4 groups (n = 10/group). Each group was treated with: 1) HMW4 (“test”); 2) raHMW4 (randomized control peptide) (“control”); 3) depletion of the HMW4-specific B cells (to prevent the production of anti-HMW4 IgM), followed by the immunization (control for B cell dependence); or 4) none. At 12 weeks of age, mice were fed a western type diet (WTD) for 12 weeks. Lesions in treated mice were then quantified, by both en face analysis of the aortic arch and morphometric analysis of ORO-stained sections of the aortic root. The “test” group showed reduction in atherosclerosis (by ~40%), when compared to the “control” group (p = 0.006) or non-treated group (p = 0.01). Such reduction was diminished when the anti-HMW4 IgM-producing B cells were depleted (p = 0.02). This study raises the possibility to amplify the anti-HMGB1 IgM response to reduce atherosclerosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.