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Integrative single-cell sequencing and metabolomics reveal the immunometabolic regulatory network of alirocumab in atherosclerosis: Focus on the PCSK9-LOX-1-NF-κB-IL-6 axis and therapeutic prospects
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DOI：10.1016/j.lddd.2026.100280.png)
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Abstract
En 中文
Atherosclerosis (AS), the primary pathological basis for cardiovascular diseases, is characterized by a maladaptive interplay between lipid deposition and chronic inflammation. Although conventional lipid-lowering therapies such as statins effectively reduce low-density lipoprotein cholesterol (LDL-C), approximately 30 % of patients continue to experience recurrent cardiovascular events, underscoring the critical need for anti-inflammatory interventions. While the non-lipid-lowering effects of PCSK9 inhibitors like alirocumab are increasingly recognized, their specific immunometabolic mechanisms remain incompletely defined. This review integrates single-cell RNA sequencing (scRNA-seq) and metabolomics to systematically elucidate how alirocumab remodels the vascular inflammatory microenvironment via the PCSK9-LOX-1-NF-kappa B-IL-6 signaling axis. It highlights its regulation of macrophage polarization (M1/M2 balance) and discusses the therapeutic potential of targeting the PCSK9-lipoprotein(a)-inflammation triad, proposing a novel framework for precision medicine in AS.
Keywords:
Atherosclerosis
Alirocumab
Proprotein COnvertase Subtilisin/kexin Type 9
Single-cell RNA sequencing
Metabolomics
PCSK9-LOX-1-NF-kappa B-IL-6 signaling axis
Journal
L
IF:
1.6
Papers:
50
Citations:
0
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Cited Papers