Macromolecular transport in heart valves. I. Studies of rat valves with horseradish peroxidase.

The present study aims to experimentally elucidate subtle structural features of the rat valve leaflet and the related nature of macromolecular transport across its endothelium and in its subendothelial space, information necessary to construct a rational theoretical model that can explain observation. After intravenous injection of horseradish peroxidase (HRP), we perfusion-fixed the aortic valve of normal Sprague-Dawley rats and found under light microscopy that HRP leaked through the leaflet's endothelium at very few localized brown spots, rather than uniformly. These spots grew nearly as rapidly with HRP circulation time before euthanasia as aortic spots, particularly when the time axis only included the time the valve was closed. These results suggest that macromolecular transport in heart valves depends not only on the direction normal to, but also parallel to, the endothelial surface and that convection, as well as molecular diffusion, plays an important role in macromolecular transport in heart valves. Transmission electron microscopy of traverse leaflet sections after 4-min HRP circulation showed a very thin ( approximately 150 nm), sparse layer immediately beneath the endothelium where the HRP concentration was much higher than that in the matrix below it. Nievelstein-Post et al.'s (Nievelstein-Post P, Mottino G, Fogelman A, Frank J. Arterioscler Thromb 14: 1151-1161, 1994) ultrarapid freezing/rotary shadow etching of the normal rabbit valve's subendothelial space supports the existence of this very thin, very sparse "valvular subendothelial intima," in analogy to the vascular subendothelial intima.

[1]  D. Rumschitzki,et al.  Macromolecular transport in heart valves. II. Theoretical models. , 2007, American journal of physiology. Heart and circulatory physiology.

[2]  Neelesh Jain,et al.  Endothelium and valvular diseases of the heart , 2003, Microscopy research and technique.

[3]  J. Frank,et al.  Sequestration of aggregated LDL by macrophages studied with freeze-etch electron microscopy. , 2001, Journal of lipid research.

[4]  D. Newby,et al.  Association between calcific aortic stenosis and hypercholesterolemia: Is there a need for a randomized controlled trial of cholesterol‐lowering therapy? , 2001, Clinical cardiology.

[5]  H. Sinzinger,et al.  Accumulation of oxidized LDL in human semilunar valves correlates with coronary atherosclerosis. , 2000, Cardiovascular research.

[6]  JanNilsson,et al.  Presence of Oxidized Low Density Lipoprotein in Nonrheumatic Stenotic Aortic Valves , 1999 .

[7]  Sheldon Weinbaum,et al.  1997 Whitaker Distinguished Lecture: Models to Solve Mysteries in Biomechanics at the Cellular Level; A New View of Fiber Matrix Layers , 1998, Annals of Biomedical Engineering.

[8]  Bonnie K. Lind,et al.  Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. , 1997, Journal of the American College of Cardiology.

[9]  Catherine M. Otto,et al.  Clinical Factors Associated With Calcific Aortic Valve Disease , 1997 .

[10]  S. Weinbaum,et al.  A fiber matrix model for the growth of macromolecular leakage spots in the arterial intima. , 1994, Journal of biomechanical engineering.

[11]  A. Fogelman,et al.  An ultrastructural study of lipoprotein accumulation in cardiac valves of the rabbit. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[12]  J. Nilsson The Early Atherosclerotic Lesion — Morphology and Mechanisms , 1993 .

[13]  G. Truskey,et al.  Measurement of endothelial permeability to 125I-low density lipoproteins in rabbit arteries by use of en face preparations. , 1992, Circulation research.

[14]  An-Li Huang,et al.  Role of intercellular junctions in the passage of horseradish peroxidase across aortic endothelium. , 1992, Laboratory investigation; a journal of technical methods and pathology.

[15]  S. Weinbaum,et al.  A new view of convective-diffusive transport processes in the arterial intima. , 1991, Journal of biomechanical engineering.

[16]  E. Vasile,et al.  An ultrastructural study of beta-very low density lipoprotein uptake and transport by valvular endothelium of hyperlipidemic rabbits. , 1991, Journal of submicroscopic cytology and pathology.

[17]  P. Chuang,et al.  Macromolecular transport across arterial and venous endothelium in rats. Studies with Evans blue-albumin and horseradish peroxidase. , 1990, Arteriosclerosis.

[18]  A. Fogelman,et al.  Ultrastructure of the intima in WHHL and cholesterol-fed rabbit aortas prepared by ultra-rapid freezing and freeze-etching. , 1989, Journal of lipid research.

[19]  M. Yarmush,et al.  Macromolecular Transport within Heart Valves , 1989, Circulation research.

[20]  S. Weinbaum,et al.  Transendothelial Transport of Low Density Lipoprotein in Association with Cell Mitosis in Rat Aorta , 1989, Arteriosclerosis.

[21]  S. Parthasarathy,et al.  A macrophage receptor that recognizes oxidized low density lipoprotein but not acetylated low density lipoprotein. , 1989, The Journal of biological chemistry.

[22]  S. Weinbaum,et al.  Enhanced macromolecular permeability of aortic endothelial cells in association with mitosis. , 1988, Atherosclerosis.

[23]  M. Simionescu,et al.  Cellular events in the development of valvular atherosclerotic lesions induced by experimental hypercholesterolemia. , 1987, Atherosclerosis.

[24]  N. Simionescu,et al.  Prelesional events in atherogenesis. Colocalization of apolipoprotein B, unesterified cholesterol and extracellular phospholipid liposomes in the aorta of hyperlipidemic rabbit. , 1987, Atherosclerosis.

[25]  N. Simionescu,et al.  Prelesional events in atherogenesis. Accumulation of extracellular cholesterol-rich liposomes in the arterial intima and cardiac valves of the hyperlipidemic rabbit. , 1986, The American journal of pathology.

[26]  E. Morrel,et al.  Local Variation in Arterial Wall Permeability to Low Density Lipoprotein in Normal Rabbit Aorta , 1986, Arteriosclerosis.

[27]  D. Morel,et al.  Monocytes and Neutrophils Oxidize Low Density Lipoprotein Making It Cytotoxic , 1985, Journal of leukocyte biology.

[28]  S. Weinbaum,et al.  Effect of cell turnover and leaky junctions on arterial macromolecular transport. , 1985, The American journal of physiology.

[29]  M. Lever,et al.  Filtration through damaged and undamaged rabbit thoracic aorta. , 1984, The American journal of physiology.

[30]  D. Morel,et al.  Endothelial and Smooth Muscle Cells Alter Low Density Lipoprotein In Vitro by Free Radical Oxidation , 1984, Arteriosclerosis.

[31]  D. Steinberg,et al.  Enhanced Macrophage Degradation of Biologically Modified Low Density Lipoprotein , 1983, Arteriosclerosis.

[32]  K. Walton,et al.  The pathogenesis of atherosclerosis of the mitral and aortic valves , 1970, The Journal of pathology.

[33]  D. Steinberg,et al.  Role of oxidised low density lipoprotein in atherogenesis. , 1993, British heart journal.

[34]  P. Libby,et al.  Involvement of the immune system in human atherogenesis: current knowledge and unanswered questions. , 1991, Laboratory investigation; a journal of technical methods and pathology.

[35]  S. Weinbaum,et al.  The role of arterial endothelial cell mitosis in macromolecular permeability. , 1988, Advances in experimental medicine and biology.