Receptor-mediated vs fluid-phase transcytosis of LDL

I read with great interest the Editorial by Kakava et al. [ [1] Kakava S. von Eckardstein A. Robert J. Regulation of low-density lipoprotein transport through endothelial cells by caveolae. Atherosclerosis. 2023; S0021–9150: 154-155 Google Scholar ] summarising evidence for caveolin 1-dependent vesicular transport of low density lipoprotein (LDL) across endothelium. Whether such large particles cross predominantly though dysfunctional intercellular junctions or via a transcellular route has been debated for decades. Evidence supporting the transcellular route includes direct visualisation of transport pathways in vitro: tracers having the size of albumin or high density lipoprotein crossed between cells, but an LDL-sized tracer was transported across cells [ [2] Ghim M. Alpresa P. Yang S.W. Braakman S.T. Gray S.G. Sherwin S.J. van Reeuwijk M. Weinberg P.D. Visualization of three pathways for macromolecule transport across cultured endothelium and their modification by flow. Am. J. Physiol. Heart Circ. Physiol. 2017; 313: H959-H973 Crossref PubMed Scopus (29) Google Scholar ].