LDL Transcytosis by the Arterial Endothelium-Atherosclerosis by a Thousand Cuts?
Level 5 - mechanism / opinion, no new human data
Narrative review of mechanistic and preclinical research without new human clinical data
PubMed 37358804 · doi:10.1007/s11883-023-01118-x
What was done
The authors reviewed recent mechanistic literature and imaging methods—specifically total internal reflection fluorescence (TIRF) live-cell microscopy—regarding how low-density lipoprotein (LDL) undergoes transcytosis across intact arterial endothelial monolayers, and evaluated potential pathways for therapeutic manipulation.
What was found
The abstract provides no quantitative data or effect sizes. Qualitatively, it reports that LDL transcytosis is mediated by scavenger receptor class B type I (SR-BI) and activin receptor-like kinase 1 (ALK1). Transcytosis via ALK1 is independent of kinase activity and antagonized by its canonical ligand, BMP9. Transcytosis is promoted by the nuclear protein HMGB1 and inflammatory signaling, whereas estrogen downregulates SR-BI and inhibits LDL transcytosis.
Why it matters
Clarifying the molecular receptors and regulators of endothelial LDL transcytosis identifies potential pharmacological targets to block initial intimal LDL accumulation in atherosclerosis.
Limits
The abstract describes a narrative review without systematic search criteria or study counts. Findings rely primarily on in vitro and preclinical mechanistic models, and no human clinical outcome data or quantitative metrics are reported.
Cited by
- contradicts The endothelial spaces in the inner layer of the arterial wall are large enough for almost any size or shape of LDL particle to penetrate.