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Local Intimal‐Medial Uptakes of 125I‐Albumin,125 I‐LDL, and Parenteral Evans Blue Dye Protein Complex Along the Aortas of Normocholesterolemic Minipigs as Predictors of Subsequent Hypercholesterolemic Atherogenesis

 

作者: Donald Fry,   Edward Herderick,   David Johnson,  

 

期刊: Arteriosclerosis and Thrombosis: A Journal of Vascular Biology  (OVID Available online 1993)
卷期: Volume 13, issue 8  

页码: 1193-1204

 

ISSN:1049-8834

 

年代: 1993

 

出版商: OVID

 

关键词: atheroma;atherosclerosis;arterial mass transport;blood pressure;endothelium;endothelial injury;endothelial permeability;fatty streaks;hypertension;intima;intimal tissue risk factor;LDL;media;mathematical models;plasma macromolecules;serum proteins;sudanop

 

数据来源: OVID

 

摘要:

This report describes the normalized intimal-medial uptakes [uptake {M, mg • cm~2)-r-serum concentration (c0, mg • cm"3)] of 125I-albumin, l25I-low-density lipoprotein (LDL), and in vivo Evans blue dye (EBD)-albumin complex as functions of pressure (P), time (t), molecular species (i), and location (z) along a ventral longitudinal z axis of the normal, intact, aortic endothelial surface in adult normocholesterolemic Sinclair Research Farm (SRF) minipigs and compares these uptake (A//c0) measurements with atherogenesis in hypercholesterolemic cohorts. Uptakes of porcine serum 125I-albumin (n=21) and 125I-LDL (n=10) were measured in freshly excised, metabolically supported aortas using a recently developed organ-support system. In vivo intimal-medial EBD uptake vs z data were measured photometrically on opened descending aortas from another group (n=6) of normocholesterolemic, adult, SRF minipigs 18 hours after the intravenous administration of EBD. For comparison purposes, the corresponding incidence of atherosclerotic lesions along the aortic z axis was calculated using topographic data from hypercholesterolemic minipig cohorts (n=39). The results showed that uptakes varied greatly with t, z, and macromolecule (i) but not with P. More specifically, the value of Af/c0 at any location (z) rose with t, was insensitive to P, decreased with macromolecular (i) size, and varied with z in a pattern that "peaked" in the upstream region, decreased to a nadir in the downstream region, and then rose again as it approached the abdominal celiac orifice. The spatially z-averaged uptake rates for the three different labeled serum proteins were 0.31 × 10"' cm • IT1 for 12SI-albumin, 0.42 × 10"' cm • h"1 for EBD-albumin, and 0.04 × 10"' cm • h"1 for 12SI-LDL. Nondimensionalized analysis of the individual sets of uptake data indicated that the overall uptake relationship [A/(t,P,z, >)/c,o, cm] could be characterized empirically by the simple product of two separate functions: one, a "scaling function" [m(z,i)], that described the uptake magnitude for a given i and z and appeared to be independent of t or P; the other, a "shape function" O(t,P)], that described the shapes of the uptake vs t and P relationships and appeared to be independent of z or i. The "scaling function" [m(z,i)] vs z contour appeared to correlate well with the corresponding atherosclerotic lesion incidence vs z contour from the group of hypercholesterolemic minipig cohorts. Assuming passive transport, it was shown ("Appendix") that m(z,i) can be interpreted physically in terms of an endothelial diffusive permeability coefficient (9/ cm • s"1). We conclude that (1) transport of albumin and LDL across the intact, normocholesterolemic, aortic endothelial surface is independent of pressure; (2) in vivo intimal-medial uptake of EBD can be used as a reasonable measure of 125I-albumin uptake; and (3) intimal-medial uptake rates of l2:I-albumin, I25I-LDL, and in vivo EBD in the normocholesterolemic state correlate with the local probability of subsequent atherogenesis in the hypercholesterolemic state.

 

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