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

Zhongqing Zeng, Patricia Nievelstein-Post, Yongyi Yin, Kung Ming Jan, Joy S. Frank, David S. Rumschitzki

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Heart Valves
Liposomes
Rabbits
Freeze Etching
Cholesterol
Lipids
Phagocytosis
Polymerization
Freezing
Extracellular Matrix
Macrophages

Keywords

  • Aortic stenosis
  • Kinetics of lipid accumulation in values
  • Size distribution

ASJC Scopus subject areas

  • Physiology

Cite this

Macromolecular transport in heart valves. III. Experiment and theory for the size distribution of extracellular liposomes in hyperlipidemic rabbits. / Zeng, Zhongqing; Nievelstein-Post, Patricia; Yin, Yongyi; Jan, Kung Ming; Frank, Joy S.; Rumschitzki, David S.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 292, No. 6, 06.2007.

Research output: Contribution to journalArticle

Zeng, Zhongqing ; Nievelstein-Post, Patricia ; Yin, Yongyi ; Jan, Kung Ming ; Frank, Joy S. ; Rumschitzki, David S. / Macromolecular transport in heart valves. III. Experiment and theory for the size distribution of extracellular liposomes in hyperlipidemic rabbits. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 292, No. 6.
@article{9dca9e4969ba48a58ce984e008f6f86e,
title = "Macromolecular transport in heart valves. III. Experiment and theory for the size distribution of extracellular liposomes in hyperlipidemic rabbits",
abstract = "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.",
keywords = "Aortic stenosis, Kinetics of lipid accumulation in values, Size distribution",
author = "Zhongqing Zeng and Patricia Nievelstein-Post and Yongyi Yin and Jan, {Kung Ming} and Frank, {Joy S.} and Rumschitzki, {David S.}",
year = "2007",
month = "6",
doi = "10.1152/ajpheart.00606.2006",
language = "English (US)",
volume = "292",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "6",

}

TY - JOUR

T1 - Macromolecular transport in heart valves. III. Experiment and theory for the size distribution of extracellular liposomes in hyperlipidemic rabbits

AU - Zeng, Zhongqing

AU - Nievelstein-Post, Patricia

AU - Yin, Yongyi

AU - Jan, Kung Ming

AU - Frank, Joy S.

AU - Rumschitzki, David S.

PY - 2007/6

Y1 - 2007/6

N2 - 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.

AB - 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.

KW - Aortic stenosis

KW - Kinetics of lipid accumulation in values

KW - Size distribution

UR - http://www.scopus.com/inward/record.url?scp=34447498758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447498758&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00606.2006

DO - 10.1152/ajpheart.00606.2006

M3 - Article

C2 - 17237250

AN - SCOPUS:34447498758

VL - 292

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 6

ER -