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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/H2687    most recent 00606.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Zeng, Z. Articles by Rumschitzki, D. S. Search for Related Content PubMed PubMed Citation Articles by Zeng, Z. Articles by Rumschitzki, D. S.

Macromolecular transport in heart valves. III. Experiment and theory for the size distribution of extracellular liposomes in hyperlipidemic rabbits

¹Department of Chemical Engineering and ³Department of Mechanical Engineering, City College of the City University of New York, New York, New York; ²Department of Medicine, UCLA School of Medicine, Los Angeles, California; and ⁴Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York

Submitted 9 June 2006 ; accepted in final form 16 January 2007

The heart valve leaflets of 29-day cholesterol-fed rabbits were examined by ultrarapid freezing without conventional chemical fixation/processing, followed by rotary shadow freeze-etching. This procedure images the leaflets' subendothelial extracellular matrix in extraordinary detail, and extracellular lipid liposomes, from 23 to 220 nm in diameter, clearly appear there. These liposomes are linked to matrix filaments and appear in clusters. Their size distribution shows 60.7% with diameters 23–69 nm, 31.7% between 70 and 119 nm, 7.3% between 120 and 169 nm, and 0.3% between 170 and 220 nm (superlarge) and suggests that smaller liposomes can fuse into larger ones. We couple our model from Part II of this series (Zeng Z, Yin Y, Jan KM, Rumschitzki DS. Am J Physiol Heart Circ Physiol 292: H2671–H2686, 2007) for lipid transport into the leaflet to the nucleation-polymerization model hierarchy for liposome formation proposed originally for aortic liposomes to predict liposome formation/growth in heart valves. Simulations show that the simplest such model cannot account for the observed size distribution. However, modifying this model by including liposome fusing/merging, using parameters determined from aortic liposomes, leads to predicted size distributions in excellent agreement with our valve data. Evolutions of both the liposome size distribution and total liposome mass suggest that fusing becomes significant only after 2 wk of high lumen cholesterol. Inclusion of phagocytosis by macrophages limits the otherwise monotonically increasing total liposome mass, while keeping the excellent fit of the liposome size distribution to the data.

aortic stenosis; kinetics of lipid accumulation in values; size distribution