Macromolecular transport within heart valves.

Abstract

The present study documents the permeability characteristics of heart valvular endothelium to low-density lipoprotein (LDL), albumin, and horseradish peroxidase (HRP). Using quantitative autoradiography, LDL and albumin concentrations were measured within aortic valves of squirrel monkeys and rabbits after 30 minutes of in vivo circulation. The valvular concentration profiles were analyzed using theoretical mathematical models based on fundamental transport principles. In vivo transvalvular concentration profiles of LDL and albumin displayed the highest tissue concentrations immediately beneath the endothelium and displayed the lowest concentrations near the midline of the valve. Tissue concentrations of LDL and albumin displayed large differences in magnitudes between different regions of individual valve leaflets suggesting marked spatial variation in the permeability properties of the valvular endothelium to LDL and albumin; this was also seen visually with HRP. The results of the theoretical analysis showed that 1) the aortic valvular endothelium limits the uptake of LDL and albumin into the valvular tissue, 2) the permeability of the valvular endothelium differs widely from one region of a valve to another and even from one side of the valve to the other within a single valvular region, and 3) intramural diffusion is the predominant mode of transport for LDL and albumin within the aortic valve, even in valvular regions exposed to large pressure differences across the valve. (Circulation Research 1989;64:1213-1223)

Macromolecular transport in heart valves. II. Theoretical models

“…46), rather than a uniform brown staining. For rats, this contradicts the earlier model's (34) first assumption and indicates that macromolecular transport in heart valves depends on the direction parallel to, as well as the direction normal to, the endothelium, i.e., transport is at least two-dimensional (2D).…”

“…Tompkins et al (34) performed the first, and thus far only, detailed measurements of such transport by using quantitative autoradiography to examine the transvalvular 125 I-LDL concentration profiles in the aortic valves of squirrel monkeys as a function of the depth into the leaflet after 30-min 125 I-LDL circulation in vivo (see Fig. 1).…”

“…Rather than using a very different set of parameters for each transvalvular LDL concentration profile as in Ref. 34, we use a single parameter set to rationally explain all of Fig. 1's experimental monkey profiles.…”

Hemodynamic and Cellular Response Feedback in Calcific Aortic Valve Disease

“…For example, VlvECs are more permeable than the ECs of major arteries, 50 with focal regions of high and low permeability 50,51 that may be responsible for focal lesion development during early stages of disease. 52 Similar to vascular disease, valvular disease is associated with inflammation, including systemic endothelial dysfunction 53 and increased expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin by VlvECs.…”

A theory for water and macromolecular transport in the pulmonary artery wall with a detailed comparison to the aorta

“…We (78) proposed a 2-D convectiondiffusion model that included these intimae, fit (only) three parameters (to a single experiment), and measured or took from the aorta all other parameters. The model explained the spot data (78) and a multitude of previously perplexing data on 125 I-LDL valve penetration (60). Combining this LDL transport with the liposome kinetics (all parameters fixed) of Yin et al (72) predicted lipid accumulation and extracellular lipid liposome size distributions in rabbits fed a high lipid diet for 1 mo in excellent agreement with the experimental liposome size distribution (75).…”