Objective:

To identify carotid plaque candidate genes and evaluate their therapeutic potential using genetic and transcriptomic approaches.

Approach:

Key Findings:

• 22candidategenesforcarotidplaquewereidentified.LIPA_Mono_Cshowedaconsistentcausalassociationwithincreasedcarotidplaquerisk.LIPAwashighlyexpressedinmononuclearphagocytesofcarotidplaquetissues.Invitroexperimentsconfirmedthatoxidizedlow-densitylipoproteinupregulatedLIPAinmacrophages.LIPAknockdownalleviatedlipidaccumulationandsuppressedcomplementactivation.InsilicoknockoutofLIPArevealedsignificantenrichmentofthecomplementandcoagulationcascades,andCellChatanalysissuggestedapotentialSPP1-CD44-mediatedinteractionbetweenLIPA-expressingmononuclearphagocytesandTcells.

Interpretation:

LIPA may be associated with lipid accumulation, complement-related activation, and immune regulation in carotid plaque, but these findings require further validation.

Limitations:

• FurthervalidationisneededtoconfirmthetranslationalrelevanceofLIPA-relatedmodulation.Thestudyprimarilyfocusesongeneticandtranscriptomicdatawithoutextensiveclinicalvalidation.

Conclusion:

The study prioritizes LIPA as a candidate gene for carotid plaque, suggesting its role in lipid metabolism and immune regulation, pending further validation.

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