The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Marc S. Penn - One of the best experts on this subject based on the ideXlab platform.
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alterations in Internal Elastic Lamina permeability as a function of age and anatomical site precede lesion development in apolipoprotein e null mice
Circulation Research, 2005Co-Authors: Kwangdeok Lee, Farhad Forudi, Gerald M. Saidel, Marc S. PennAbstract:Early atherosclerosis is characterized by the accumulation of plasma-borne macromolecules (eg, low-density lipoproteins) in the arterial intima, which is bordered by endothelial cells (EC) and the Internal Elastic Lamina (IEL). This accumulation is believed to be secondary to increased EC permeability. We hypothesized that a decrease in IEL permeability may precede lesion development and contribute to macromolecular accumulation. To test this hypothesis, we quantified EC and IEL permeability in lesion-free areas of the thoracic and abdominal aortas of chow-fed C57BL/6 control and atherosclerotic-prone apolipoprotein E (apoE)-null mice at 3 and 5 months of age. Between 3 and 5 months of age, apoE-null mice begin to develop atherosclerotic lesions in the thoracic aorta. No significant differences in EC and IEL permeability were observed at either time in C57BL/6 control mice. In contrast, 78% and 19% decreases in IEL permeability of the thoracic aorta and abdominal aorta, respectively, were observed between 3 to 5 months of age in apoE-null mice (thoracic: 2.05+/-1.33 and 0.44+/-0.15 microm/min, P<0.001; abdominal: 1.13+/-0.58 and 0.93+/-0.44 microm/min, P<0.05). To further determine whether decreased IEL permeability is linked with atherosclerotic lesion development, we quantified IEL permeability in the greater and lesser curvature of the aortic arch. In apoE-null mice, the lesser curvature of the aortic arch develops lesions before the greater curvature. We found a significant and sustained decrease (59%) in IEL permeability in the lesser curvature of the aortic arch compared with the greater curvature. These data suggest that atherogenesis involves the pathological remodeling of the IEL, not the endothelium before lesion development. This remodeling may be attributable to local responses of the endothelium and smooth muscle cells to hyperlipidemia.
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Alterations in Internal Elastic Lamina Permeability As a Function of Age and Anatomical Site Precede Lesion Development in Apolipoprotein E–Null Mice
Circulation Research, 2005Co-Authors: Kwangdeok Lee, Farhad Forudi, Gerald M. Saidel, Marc S. PennAbstract:Early atherosclerosis is characterized by the accumulation of plasma-borne macromolecules (eg, low-density lipoproteins) in the arterial intima, which is bordered by endothelial cells (EC) and the Internal Elastic Lamina (IEL). This accumulation is believed to be secondary to increased EC permeability. We hypothesized that a decrease in IEL permeability may precede lesion development and contribute to macromolecular accumulation. To test this hypothesis, we quantified EC and IEL permeability in lesion-free areas of the thoracic and abdominal aortas of chow-fed C57BL/6 control and atherosclerotic-prone apolipoprotein E (apoE)-null mice at 3 and 5 months of age. Between 3 and 5 months of age, apoE-null mice begin to develop atherosclerotic lesions in the thoracic aorta. No significant differences in EC and IEL permeability were observed at either time in C57BL/6 control mice. In contrast, 78% and 19% decreases in IEL permeability of the thoracic aorta and abdominal aorta, respectively, were observed between 3 to 5 months of age in apoE-null mice (thoracic: 2.05+/-1.33 and 0.44+/-0.15 microm/min, P
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Relative significance of endothelium and Internal Elastic Lamina in regulating the entry of macromolecules into arteries in vivo.
Circulation research, 1994Co-Authors: Marc S. Penn, Gerald M. Saidel, Guy M. ChisolmAbstract:A role for the Internal Elastic Lamina (IEL), which separates the intima and media of an artery wall, as a restrictive barrier to macromolecular movement has been suggested in atherosclerotic lesion development or restenosis during angioplasty. The permeability coefficient of the IEL, however, has never been quantified in unperturbed vessels in vivo. Using a newly developed technique, we measured the concentration distributions in both intima and media of cationic (pI approximately 8.5) and anionic (pI approximately 6.3) isozymes of the 44-kD macromolecule horseradish peroxidase (HRP). Two mathematical models of arterial wall transport differing in their resolution of the intima were required to simulate the concentration distribution data and to estimate the parameters of interest. Optimal estimates of the permeability coefficients of the endothelium (PE) and IEL (PIEL) to HRP were determined by the best least-squares fit of the two models to experimental data. These estimates (anionic: PE = 0.050 +/- 0.021 microns/min, PIEL = 0.146 +/- 0.082 microns/min, n = 8; cationic: PE = 0.034 +/- 0.018 microns/min, PIEL = 0.110 +/- 0.047 microns/min, n = 8) indicate that the IEL is responsible for approximately 25% (anionic, 26 +/- 9%; cationic, 25 +/- 13%) of the resistance to HRP transport from the blood into the arterial media. Although both parameters were less for the cationic preparation, the differences were not significant, and the relative role of the IEL was similar for both molecules.(ABSTRACT TRUNCATED AT 250 WORDS)
M Osborne-pellegrin - One of the best experts on this subject based on the ideXlab platform.
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Rupture of the Internal Elastic Lamina and vascular fragility in stroke-prone spontaneously hypertensive rats.
Stroke, 1991Co-Authors: M Coutard, M Osborne-pellegrinAbstract:We studied a possible relation between stroke and an enhanced susceptibility to rupture of the arterial Internal Elastic Lamina by comparing stroke-prone spontaneously hypertensive rats with spontaneously hypertensive rats, which have a very low incidence of stroke. We quantified interruptions in the Internal Elastic Lamina in certain arteries and studied the effect of beta-aminopropionitrile, an inhibitor of cross-link formation in collagen and Elastic fibers, on rupture of the Internal Elastic Lamina and on mortality in these two substrains. To eliminate any influence of higher blood pressure in the stroke-prone rats on the parameters studied, we used antihypertensive treatment to obtain equivalent blood pressures in the two substrains. Results showed that stroke sensitivity was associated with an enhanced early spontaneous rupture of the Internal Elastic Lamina in the caudal artery, an increased susceptibility to beta-aminopropionitrile-induced rupture of the Internal Elastic Lamina, and earlier mortality, mainly from aortic rupture, under beta-aminopropionitrile treatment. These findings suggest that stroke-prone rats have an enhanced minor connective tissue defect that is expressed by rupture of the Internal Elastic Lamina and may be related, at least in part, to their greater vascular fragility and increased susceptibility to stroke.
John M. Tarbell - One of the best experts on this subject based on the ideXlab platform.
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Internal Elastic Lamina affects the distribution of macromolecules in the arterial wall a computational study
American Journal of Physiology-heart and Circulatory Physiology, 2004Co-Authors: Shigeru Tada, John M. TarbellAbstract:The Internal Elastic Lamina (IEL), which separates the arterial intima from the media, affects macromolecular transport across the medial layer. In the present study, we have developed a two-dimens...
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Internal Elastic Lamina affects the distribution of macromolecules in the arterial wall: a computational study.
American journal of physiology. Heart and circulatory physiology, 2004Co-Authors: Shigeru Tada, John M. TarbellAbstract:The Internal Elastic Lamina (IEL), which separates the arterial intima from the media, affects macromolecular transport across the medial layer. In the present study, we have developed a two-dimensional numerical simulation model to resolve the influence of the IEL on convective-diffusive transport of macromolecules in the media. The model considers interstitial flow in the medial layer that has a complex entrance condition because of the presence of leaky fenestral pores in the IEL. The IEL was modeled as an impermeable barrier to both water and solute except for the fenestral pores that were assumed to be uniformly distributed over the IEL. The media were modeled as a heterogeneous medium composed of an array of smooth muscle cells (SMCs) embedded in a continuous porous medium representing the interstitial proteoglycan and collagen fiber matrix. Results for ATP and low-density lipoprotein (LDL) demonstrate a range of interesting features of molecular transport and uptake in the media that are determined by considering the balance among convection, diffusion, and SMC surface reaction. The ATP concentration distribution depends strongly on the IEL pore structure because ATP fluid-phase transport is dominated by diffusion emanating from the fenestral pores. On the other hand, LDL fluid-phase transport is only weakly dependent on the IEL pore structure because convection spreads LDL laterally over very short distances in the media. In addition, we observe that transport of LDL to SMC surfaces is likely to be limited by the fluid phase (surface concentration less than bulk concentration), whereas ATP transport is limited by reaction on the SMC surface (surface concentration equals bulk concentration).
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Fenestral Pore Size in the Internal Elastic Lamina Affects Transmural Flow Distribution in the Artery Wall
Annals of Biomedical Engineering, 2001Co-Authors: Shigeru Tada, John M. TarbellAbstract:Interstitial flow through the subendothelial intima and media of an artery wall was simulated numerically to investigate the water flow distribution through fenestral pores which affects the wall shear stress on smooth muscle cells right beneath the Internal Elastic Lamina (IEL). A two-dimensional analysis using the Brinkman model of porous media flow was performed. It was observed that the hydraulic permeability of the intimal layer should be much greater than that of the media in order to predict a reasonable magnitude for the pressure drop across the subendothelial intima and IEL (about 23 mostly at a 70 mm Hg luminal pressure). When K_i was set equal to the value in the media, this pressure drop was unrealistically high. Furthermore, the higher value of K_i produced a nearly uniform distribution of water flow through a simple array of fenestral pores all having the same diameters (1.2 μm), whereas when K_i was set at the value in the media, the flow distribution through fenestral pores was highly nonuniform and nonphysiologic. A deformable intima model predicted a nonuniform flow distribution at high pressure (180 mm Hg). Damage to the IEL was simulated by introducing a large fenestral pore (up to 17.8 μm) into the array. A dramatic increase in flow through the large pore was observed implying an altered fluid mechanical environment on the smooth muscle cells near the large pore which has implications for intimal hyperplasia and atherosclerosis. The model also predicted that the fluid shear stress on the bottom surface of an endothelial cell is on the order of 10 dyne/cm^2 a level which can affect cell function. © 2001 Biomedical Engineering Society. PAC01: 8719Tt, 8380Lz, 8716Uv, 8719Ff
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Interstitial flow through the Internal Elastic Lamina affects shear stress on arterial smooth muscle cells
American journal of physiology. Heart and circulatory physiology, 2000Co-Authors: Shigeru Tada, John M. TarbellAbstract:Interstitial flow through the tunica media of an artery wall in the presence of the Internal Elastic Lamina (IEL), which separates it from the subendothelial intima, has been studied numerically. A...
Terho Lehtimäki - One of the best experts on this subject based on the ideXlab platform.
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Methylenetetrahydrofolate reductase gene C677T mutation is related to the defects in the Internal Elastic Lamina of the artery wall.
European journal of clinical investigation, 2002Co-Authors: Päivi Hämelahti, Otso Järvinen, T. Sisto, Erkki Ilveskoski, Valtteri Wirta, Timo Koivula, Terho LehtimäkiAbstract:Background The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene leads to C/C, C/T and T/T genotypes, which affect the plasma homocysteine concentration in humans. In mini-pigs, high serum homocysteine levels are associated with defects in the Internal Elastic Lamina (IEL) of the artery wall, which are apparently related to the migration of smooth muscle cells into the intima during atherogenesis. We studied the association between the MTHFR genotypes and the number of gaps in the IEL in the wall of the five major abdominal arteries. Materials and methods The autopsy study included 123 subjects (90 males and 33 females) aged 18–93. For the light microscopy, a 0·5 cm circular segment of the coeliac, the superior mesenteric, the inferior mesenteric and the renal arteries were cut and embedded in paraffin blocks. The circumference of the IEL, the thickness of the intima and the number of the gaps per millimetre in the IEL were measured by MOP 3 image analysis. Results The T-allele carriers (C/T and T/T) of the MTHFR gene had significantly less gaps in the IEL than the subjects with the C/C genotype in the superior mesenteric and in the left renal arteries (2·02 ± 2·25 vs. 2·53 ± 1·89, P
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methylenetetrahydrofolate reductase gene c677t mutation is related to the defects in the Internal Elastic Lamina of the artery wall
European Journal of Clinical Investigation, 2002Co-Authors: Päivi Hämelahti, Otso Järvinen, T. Sisto, Erkki Ilveskoski, Valtteri Wirta, Timo Koivula, Terho LehtimäkiAbstract:Background The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene leads to C/C, C/T and T/T genotypes, which affect the plasma homocysteine concentration in humans. In mini-pigs, high serum homocysteine levels are associated with defects in the Internal Elastic Lamina (IEL) of the artery wall, which are apparently related to the migration of smooth muscle cells into the intima during atherogenesis. We studied the association between the MTHFR genotypes and the number of gaps in the IEL in the wall of the five major abdominal arteries. Materials and methods The autopsy study included 123 subjects (90 males and 33 females) aged 18–93. For the light microscopy, a 0·5 cm circular segment of the coeliac, the superior mesenteric, the inferior mesenteric and the renal arteries were cut and embedded in paraffin blocks. The circumference of the IEL, the thickness of the intima and the number of the gaps per millimetre in the IEL were measured by MOP 3 image analysis. Results The T-allele carriers (C/T and T/T) of the MTHFR gene had significantly less gaps in the IEL than the subjects with the C/C genotype in the superior mesenteric and in the left renal arteries (2·02 ± 2·25 vs. 2·53 ± 1·89, P < 0·04 and 0·56 ± 1·09 vs. 1·82 ± 2·66, P < 0·02, respectively). The trend was similar for the coeliac and the right renal arteries. Conclusions Our result suggests that MTHFR polymorphism may be involved in the fragmentation of the IEL.
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apolipoprotein e polymorphism and atherosclerosis association of the e4 allele with defects in the Internal Elastic Lamina
Atherosclerosis, 2000Co-Authors: Erkki Ilveskoski, Otso Järvinen, T. Sisto, Pekka J. Karhunen, Pekka Laippala, Terho LehtimäkiAbstract:The defects in the Internal Elastic Lamina (IEL) have been proposed to be important for the migration of smooth muscle cells into the intima during atherosclerosis. We investigated the association of a genetic factor — apolipoprotein E (apoE) genotype — with the number of gaps in the IEL of the artery wall in 123 consecutive autopsy cases (90 male, 33 female) aged 18–93. At autopsy, the circumference of the IEL and the number of gaps in the IEL were measured in circular samples of the coeliac; (CA), superior mesenteric (SMA) and inferior mesenteric (IMA) arteries. In the series, the number of gaps per millimetre in the IEL of CA, SMA and IMA were associated with intimal thickening (P<0.0001, P=0.01 and P=0.005, respectively). In men, apoE genotype was significantly associated with the number of gaps in the IEL of the CA and IMA (P=0.033 and P=0.04 1, respectively). The carriers of e4/3 or e4/4 genotype had higher number of gaps in CA than the carriers of e3/3 genotype (2.30±2.63 vs 1.38±1.83 gaps/mm, P=0.035) and also higher number of gaps in IMA than the carriers of e3/2 (2.18±1.71 vs 0.66±0.60 gaps/mm, P=0.041). The results suggest that the apoE e4 allele may be involved with IEL fragmentation in men. This may be mediated through higher serum cholesterol associated with the e4 allele.
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Apolipoprotein E polymorphism and atherosclerosis: association of the ε4 allele with defects in the Internal Elastic Lamina
Atherosclerosis, 2000Co-Authors: Erkki Ilveskoski, Otso Järvinen, T. Sisto, Pekka J. Karhunen, Pekka Laippala, Terho LehtimäkiAbstract:The defects in the Internal Elastic Lamina (IEL) have been proposed to be important for the migration of smooth muscle cells into the intima during atherosclerosis. We investigated the association of a genetic factor — apolipoprotein E (apoE) genotype — with the number of gaps in the IEL of the artery wall in 123 consecutive autopsy cases (90 male, 33 female) aged 18–93. At autopsy, the circumference of the IEL and the number of gaps in the IEL were measured in circular samples of the coeliac; (CA), superior mesenteric (SMA) and inferior mesenteric (IMA) arteries. In the series, the number of gaps per millimetre in the IEL of CA, SMA and IMA were associated with intimal thickening (P
Amir Lerman - One of the best experts on this subject based on the ideXlab platform.
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Experimental hypercholesterolemia induces ultrastructural changes in the Internal Elastic Lamina of porcine coronary arteries
Atherosclerosis, 1998Co-Authors: Hyuck Moon Kwon, Giuseppe Sangiorgi, Luigi Giusto Spagnoli, Katsumi Miyauchi, David R. Holmes, Robert S. Schwartz, Amir LermanAbstract:The Internal Elastic Lamina (IEL) serves as a barrier for cells and macromolecules migration between the intima and the media in the vascular wall. Several investigators have reported Internal Elastic Lamina ultrastructural changes in Elastic arteries with atherosclerosis. However, no quantitative and qualitative assessment of the Internal Elastic Lamina architecture in muscular arteries such as the coronary circulation during early atherosclerosis have been performed yet. In this study, we therefore evaluated the ultrastructural morphological changes of the IEL in the coronary circulation of pigs fed with high cholesterol diet. Animals were sacrificed after being fed either a high cholesterol diet for 10-12 weeks (n = 5, 12 coronary segments) or a control diet (n = 4, 15 coronary segments). Coronary arteries were analyzed by transmission and scanning electron microscopy. In addition, computerized digital analysis of the images obtained by confocal scanning microscopy was performed for the quantitation of the morphologic changes in the Internal Elastic Lamina. Confocal microscopy and scanning electron microscopy revealed an altered pattern characterized by large oval fenestration formation in the Internal Elastic Lamina of hypercholesterolemic animals. Computerized morphometric analysis of confocal microscopy images demonstrated that compared to controls, the IEL of cholesterol-fed animals was characterized by an increase in the minor diameter of the fenestrae (2.16 +/- 0.04 microm versus 3.32 +/- 0.06 microm, P = 0.003) and a decrease in the fenestrae density (22333 +/- 1334/mm2 versus 17552 +/- 931/mm2, P = 0.015) of the Internal Elastic Lamina. The percentage of the IEL area covered by the fenestrae correlated with the intimal thickness (r = 0.79, P = 0.004). This study demonstrates that experimental hypercholesterolemia is characterized by ultrastructural changes of the Internal Elastic Lamina in the coronary circulation. This study suggests that the IEL may play an important role in the development of structural changes which characterize the early phase of coronary atherosclerosis.
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Ultrastructural changes of the Internal Elastic Lamina in experimental hypercholesterolemic porcine coronary arteries
Journal of Korean medical science, 1998Co-Authors: Hyuck Moon Kwon, Robert S. Schwartz, Dong Soo Kim, Bum-kee Hong, Ki Hyun Byun, Jun Sick Kna, Hyun-seung Kim, Amir LermanAbstract:The Internal Elastic Lamina (IEL) serves as a barrier for cells and macromolecules between the intima and media in the vascular wall. We evaluated the morphological changes and quantitative assessments of the IEL architecture in the coronary circulation of pigs fed with a high cholesterol diet. Transmission electron microscopy (TEM) analysis of the IEL from hypercholesterolemic coronary arteries revealed fragmentation of the IEL associated with a decrease in the thickness. Confocal microscopy and scanning electron microscopy (SEM) revealed an altered pattern characterized by a large oval fenestration in the IEL of hypercholesterolemic vessels. Morphometric analysis of confocal microscopy images demonstrated that the IEL of cholesterol-fed animals were characterized by an increase in the minor diameter of the fenestrae (2.16+/-0.04 microm vs 3.32+/-0.06 microm, p=0.003) and a decrease in the fenestrae density (22,333+/-1,334/mm2 vs 17,552+/-931/mm2, p=0.015) compared to controls. The percentage of the IEL area covered by the fenestrae correlated with the intimal thickness (r=0.79, p=0.004). The immunoreactivity for matrix metalloproteinase-3 (MMP-3) increased in cholesterol-fed coronary arteries, predominantly in the neointima. This study demonstrates experimental hypercholesterolemia induced ultrastructural changes of the IEL in the coronary circulation. The IEL may play an important role in the development of structural changes which characterize the early phase of coronary atherosclerosis.
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Arterial remodeling after experimental percutaneous injury is highly dependent on adventitial injury and histopathology
International journal of cardiology, 1997Co-Authors: Michael E. Staab, Giuseppe Sangiorgi, David R. Holmes, Amir Lerman, Sanjay S. Srivatsa, Myung Ho Jeong, William D. Edwards, Robert S. SchwartzAbstract:Abstract Background: The extent and nature of unfavorable geometric remodeling, especially related to the adventitia, has not been studied previously. The purpose of this study was to examine two methods of experimental arterial injury, characterize the extent of remodeling, and determine if remodeling is injury-specific. Methods: Two methods for producing coronary stenoses in pigs were used: heat injury using thermal balloon angioplasty (resulting in adventitial fibrosis), and copper stent implantation (resulting in intense inflammation). Histomorphometric parameters included changes in neointimal thickness (delta neointima) from uninjured to injured sections, and differences in area circumscribed by the Internal and external Elastic Laminas (delta Internal Elastic Lamina area and delta external Elastic Lamina area, respectively). Remodeling was calculated for each lesion as the enlargement of the external Elastic Lamina area or Internal Elastic Lamina area for incremental neointimal thickening, expressed as the slopes delta external Elastic Lamina area/delta neointima and delta Internal Elastic Lamina area/delta neointima. Results: Remodeling indices for the heat lesions were negative (delta Internal Elastic Lamina area/delta neointima=−0.15, delta external Elastic Lamina area/delta neointima=−0.64) and indicated little remodeling in contrast to copper stent injury (delta Internal Elastic Lamina area/delta neointima=0.95, delta external Elastic Lamina area/delta neointima=1.20). Conclusions: Remodeling in fibrotic compared to inflammatory lesions differs markedly, and may explain increased restenosis rates observed in thermal balloon angioplasty in patients. This formulation may be useful to study remodeling and restenosis following other interventional technologies.
