Chain-length specific ceramide biology in cardiovascular disease: from molecular diversity to precision risk stratification
Year: 2026
Type: article
Abstract: Ceramides are increasingly recognized as biomarkers and potential mediators of residual cardiovascular risk, yet their biological significance cannot be captured by total ceramide abundance alone. Individual species differ in acyl-chain length, saturation, enzymatic origin, tissue distribution, and subcellular localization, resulting in distinct and sometimes opposing cardiovascular effects. This review synthesizes biochemical, experimental, clinical, and genetic evidence through a chain-length specific framework. Long-chain ceramides, particularly Cer16:0 and Cer18:0, are consistently associated with lipotoxicity, mitochondrial dysfunction, impaired insulin signaling, endothelial injury, inflammation, plaque instability, myocardial remodeling, and adverse cardiovascular outcomes. In contrast, saturated very-long-chain species such as Cer22:0 and Cer24:0 often define a lower-risk circulating profile, although their effects remain tissue- and disease-dependent; Cer24:1 further demonstrates that saturation modifies the biological meaning of chain length. These patterns explain the prognostic value of ratios such as Cer16:0/Cer24:0 and Cer18:0/Cer24:0 and provide a biological basis for CERT1 and CERT2. We further examine ceramide synthases as determinants of species composition, distinguish circulating biomarkers from tissue-level mechanisms, and evaluate emerging genetic, causal, and therapeutic evidence. Collectively, current data support a precision lipidomic model focused on pathogenic chain-length remodeling rather than non-selective suppression of total ceramides.
Source: Frontiers in Pharmacology
Institution: Second Xiangya Hospital of Central South University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225741523