Relative significance of endothelium and internal elastic lamina in regulating the entry of macromolecules into arteries in vivo.
A role for the internal elastic lamina (IEL), which separates the intima and media of an artery wall, as a restrictive barrier to macromolecular movement has been suggested in atherosclerotic lesion development or restenosis during angioplasty. The permeability coefficient of the IEL, however, has never been quantified in unperturbed vessels in vivo. Using a newly developed technique, we measured the concentration distributions in both intima and media of cationic (pI approximately 8.5) and anionic (pI approximately 6.3) isozymes of the 44-kD macromolecule horseradish peroxidase (HRP). Two mathematical models of arterial wall transport differing in their resolution of the intima were required to simulate the concentration distribution data and to estimate the parameters of interest. Optimal estimates of the permeability coefficients of the endothelium (PE) and IEL (PIEL) to HRP were determined by the best least-squares fit of the two models to experimental data. These estimates (anionic: PE = 0.050 +/- 0.021 microns/min, PIEL = 0.146 +/- 0.082 microns/min, n = 8; cationic: PE = 0.034 +/- 0.018 microns/min, PIEL = 0.110 +/- 0.047 microns/min, n = 8) indicate that the IEL is responsible for approximately 25% (anionic, 26 +/- 9%; cationic, 25 +/- 13%) of the resistance to HRP transport from the blood into the arterial media. Although both parameters were less for the cationic preparation, the differences were not significant, and the relative role of the IEL was similar for both molecules.(ABSTRACT TRUNCATED AT 250 WORDS)
Penn
M S
MS
Department of Cell Biology, Cleveland Clinic Foundation, OH 44195.
Saidel
G M
GM
Chisolm
G M
GM
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001692:Biological Transport; D004547:Elastic Tissue / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006735:Horseradish Peroxidase; D046911:Macromolecular Substances; D008955:Models, Cardiovascular; D051381:Rats
D046911:Macromolecular Substances; D006735:Horseradish Peroxidase