Inhibition Effects of Nippostrongylus brasiliensis and Its Derivatives against Atherosclerosis in ApoE-/- Mice through Anti-Inflammatory Response

Abstract

Atherosclerosis (AS) is a dominant and growing cause of death and disability worldwide that involves inflammation from its inception to the emergence of complications. Studies have demonstrated that intervention with helminth infections or derived products could modulate the host immune response and effectively prevent or mitigate the onset and progression of inflammation-related diseases. Therefore, to understand the molecular mechanisms underlying the development of atherosclerosis, we intervened in ApoE-/- mice maintained on a high-fat diet with Nippostrongylus brasiliensis (N. brasiliensis) infection and immunized with its derived products. We found that N. brasiliensis infection and its derived proteins had suitable protective effects both in the initial and progressive stages of atherosclerosis, effectively reducing aortic arch plaque areas and liver lipid contents and downregulating serum LDL levels, which may be associated with the significant upregulation of serum anti-inflammatory cytokines (IL-10 and IL-4) and the down-regulation of proinflammatory cytokines (TNF-α and IFN-γ) in the serum. In conclusion, these data highlighted the effective regulatory role of N. brasiliensis and its derived proteins in the development and progression of atherosclerosis. This could provide a promising new avenue for the prevention and treatment of atherosclerosis.

Anti-Inflammatory Responses Produced with Nippostrongylus brasiliensis-Derived Uridine via the Mitochondrial ATP-Sensitive Potassium Channel and Its Anti-Atherosclerosis Effect in an Apolipoprotein E Gene Knockout Mouse Model

“…However, the effect of AS intervention on uridine has not been reported. In ApoE −/− mouse models, two routes of administration of ES or uridine were used for anti-atherosclerosis evaluation and significant protective effects were produced by ES and uridine, which were manifested in the induction of an anti-inflammatory environment and the alleviation of AS development, which is similar to our previous study with N. brasiliensisinfected interventions [20]. No differences were observed between different routes of administration.…”

“…Our previous study has also shown that N. brasiliensis -derived products can stimulate macrophages with M2 polarization in vitro [ 19 ]. Furthermore, in the AS model (ApoE −/− mouse on high-fat diet), N. brasiliensis infection or its derived products could induce an anti-inflammatory state and effectively inhibit the occurrence and development of AS, as evidenced by reduced aortic arch plaque areas and liver lipid contents, downregulated serum low-density lipoprotein (LDL), and upregulated anti-inflammatory cytokine levels (IL-10 and IL-4) manifested in serum [ 20 ]. However, interventions with direct helminth infection or its derived mixed products could have several concerns including ethical constraints, safety considerations, and not guaranteed effects.…”