Work

Effects of Neuraminidase-Induced Modification of LDL in the Progression of Atherosclerosis in ApoE-Knockout Mice

Year: 2026

Type: article

Abstract: BACKGROUND AND OBJECTIVES: consequences remain unclear. We investigated whether sustained LDL desialylation induced by exogenous neuraminidase promotes atherogenesis in apolipoprotein E-knockout (ApoE-KO) mice under chow and Western diet conditions. METHODS: ApoE-KO mice received neuraminidase conjugated to mouse immunoglobulin G every 5 days for 6 weeks under chow or Western diet conditions (n=40 total). LDL sialic acid content, macrophage lipid loading, aortic lesion development, serum lipid profile, and markers of systemic toxicity were assessed. RESULTS: Repeated neuraminidase administration induced sustained LDL desialylation, as shown by reduced LDL sialic acid content. LDL isolated from neuraminidase-treated ApoE-KO mice showed increased atherogenicity, reflected by greater cholesterol and lipid accumulation in RAW264.7 macrophages compared with LDL from untreated ApoE-KO mice. Neuraminidase administration increased aortic lesion area under chow diet conditions. Under chow diet conditions, neuraminidase primarily increased LDL cholesterol levels and the LDL/high-density lipoprotein ratio, while total cholesterol remained unchanged. Diet-associated elevations in liver-related biochemical markers were not exacerbated by neuraminidase treatment, and no evidence of overt renal or hematological toxicity was observed. CONCLUSIONS: and highlights sialylation pathways as potential targets in atherosclerosis.

Source: Korean Circulation Journal

DOI: 10.4070/kcj.2025.0481

Authors: Dmitry Alexandrovich Kashirskikh, Pyotr Romanovich Lebedev, Alexey Vasilievich Deykin, Gulalek Amanmyradovna Babayeva, Alexander Nikolaevich Orekhov, Igor Alexandrovich Sobenin