Curr Atheroscler Rep. 2026 May 26;28(1):56. doi: 10.1007/s11883-026-01421-3.
ABSTRACT
PURPOSE OF REVIEW: The accumulation of lipids, particularly cholesteryl esters, in the arterial intima is an early sign of atherogenesis. Although low-density lipoprotein (LDL) is the primary lipid donor in the circulation, native LDL does not induce lipid accumulation in cultured cells. However, modified forms of LDL exhibit pronounced atherogenic properties. Although LDL oxidation has traditionally been considered a key factor in atherogenicity, emerging data indicate that desialylated LDL, rather than oxidized LDL, is the predominant atherogenic form in human plasma. This review summarizes current evidence supporting LDL desialylation as the initiating event in atherogenesis and discusses its implications for therapeutic intervention.
RECENT FINDINGS: Biochemical analysis of LDL isolated from human plasma reveals that desialylation is the earliest and most important modification in the cascade leading to the formation of multiply modified LDL. Circulating sialidase, associated with extracellular vesicles, mediates this process. Pharmacological screening of over 60 compounds identified several potent sialidase inhibitors, among which epigallocatechin demonstrated the highest efficacy and a favorable safety profile. In pilot clinical studies, administration of epigallocatechin in the form of the dietary supplement Tertinat significantly increased the sialic acid content of LDL, with a sustained effect observed over a treatment period exceeding 12 months. LDL desialylation appears to be a central initiating mechanism in the development of atherogenic LDL particles. Targeting circulating sialidase activity represents a promising therapeutic strategy for the treatment of atherosclerotic cardiovascular disease. A multicenter, randomized, double-blind, placebo-controlled clinical trial, the Sialidase Inhibition as Anti-Atherosclerotic Therapy (SIAT) trial, was initiated to evaluate whether inhibiting LDL desialylation can prevent LDL modification and slow atherogenesis.
PMID:42189392 | DOI:10.1007/s11883-026-01421-3