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Am J Physiol Heart Circ Physiol (January 19, 2007). doi:10.1152/ajpheart.00606.2006
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Submitted on June 9, 2006
Accepted on January 16, 2007

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

Zhongqing Zeng1, Patricia Nievelstein - Post, Yongyi Yin, Kung-Ming Jan, Joy S Frank, and David S Rumschitzki1*

1 Department of Chemical Engineering, City College of the City University of New York, New York, New York, United States

* To whom correspondence should be addressed. E-mail: david{at}chemail.engr.ccny.cuny.edu.

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 70-119 nm, 7.3% between 120-169 nm, and 0.3%, between 170-220 nm or super-large, and suggests that smaller liposomes can fuse into larger ones. We couple our model from Part II (22) of this series 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 two weeks 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.







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