Metabolic & Cardiometabolic
LDL particle enters via receptor-mediated transcytosis
In plain terms: Does LDL enter the artery wall mainly by active transport (transcytosis) through the vessel lining?
Animal and cell evidence shows LDL crosses the artery's endothelial lining mainly by active receptor-mediated transcytosis (SR-B1/DOCK4, ALK1, caveolae), and inflammation/insulin signals can ramp this entry up.
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: Animal studies (Animal)
How the studies fall
What the evidence shows
<!-- vault-context --> Norwitz **affirms** this claim. Consensus below reflects independent literature only.
The evidence (11)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Bolanle 2025 · Arterioscler Thromb Vasc Biol | mechanism | supports | moderate | Review: LDL crosses arterial endothelium chiefly by active receptor-mediated transcytosis (SR-B1, ALK1, caveolae, ALK1), a therapeutic target. |
| Jang 2025 · Proc Natl Acad Sci U S A | in-vitro | supports | moderate | Lipid-raft proteomics identify endothelial MYH9 (myosin-9) as a regulator of LDL transcytosis — adds machinery to receptor-mediated route. |
| Cabodevilla 2026 · J Clin Invest | in-vitro | supports | moderate | ApoB N-terminus mediates atherogenic-lipoprotein binding to endothelial cells — defines ligand side of receptor-mediated LDL entry. |
| Weinberg 2022 · Front Bioeng Biotechnol | mechanism | mixed | moderate | Critical review notes transcytosis is increasingly favored but argues the relative contributions of transcytosis versus widened intercellular junctions and shear-driven permeability remain contested. |
| Huang 2019 · Nature | animal | supports | high | In mice, endothelial SR-B1 binds LDL and (via DOCK4) drives its transcytosis into the artery wall, promoting atherosclerosis. |
| Lee 2023 · Nat Cardiovasc Res | animal | supports | high | EC ALK1 deletion or anti-ALK1 antibody limits LDL transcytosis and plaque in mice without changing plasma cholesterol — receptor-mediated entry confirmed. |
| Zhang 2018 · Front Cardiovasc Med | mechanism | supports | moderate | Reviews caveolae/SR-B1/ALK1/LDLR-dependent LDL transcytosis as the mechanism delivering LDL across intact endothelium to initiate plaque. |
| Fung 2024 · J Lipid Res | in-vitro | supports | moderate | ApoA1/HDL competitively bind endothelial SR-B1 and limit LDL transcytosis — corroborates SR-B1 as a transcytosis receptor. |
| Zhang 2020 · Curr Opin Lipidol | mechanism | supports | moderate | Summarizes evidence that active transcytosis across the endothelium, not passive junctional leak, is the initial and rate-limiting step of LDL accumulation in the arterial wall. |
| Zegeye 2026 · Mol Med | in-vitro | supports | moderate | IL-6 (inflammation) enhances endothelial LDL uptake via macropinocytosis/LDL-R degradation — supports inflammatory modulation of LDL entry. |
| Goldberg 2024 · J Atheroscler Thromb | mechanism | supports | moderate | Review/commentary: lipoproteins actively cross the endothelial barrier (transcytosis) as the initiating step of atherogenesis. |
Disagree, or know a study we missed?
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Educational only, not medical advice. Grades and scores reflect published evidence weighted by study design and quality; see the methodology.