A human arterial organ culture model of postangioplasty restenosis: results up to 56 days after ballooning

Voisard, Rainer; Eicken, J. von; Baur, Regine; Gschwend, Jürgen E.; Wenderoth, U. K.; Kleinschmidt, K.; Hombach, Vinzenz; Höher, Martin

doi:10.1016/s0021-9150(99)00046-5

Cited by 24 publications

(38 citation statements)

References 49 publications

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“…This observation is in agreement with data showing inhibition of vascular smooth muscle cell proliferation when cells are cocultured with endothelial cells [25, 26, 27]and with the previously reported relationship between arterial wall damage and the extent of smooth muscle proliferation [28]. Similar results have been reported in cultured human renal arteries, in which a small proliferative activity was observed after 21 days in culture but no proliferative activity was found after 28 days [15]. Our culture period was limited to 4 weeks, as the major events of stent endothelialization occur during the first month after vascular implantation [29, 30].…”

Section: Discussionsupporting

confidence: 93%

“…Smooth muscle cells originating from the media were identified immunohistochemically in neointimal tissue. These data are concordant with the stent wall incorporation process described in animal models [30, 32]or other artery culture models [15, 33]. The adventia, which is involved in the healing process after coronary injury [10]and undergoes thickening induced by myofibroblast formation and fibrosis, was not specifically studied in our model.…”

Section: Discussionsupporting

confidence: 86%

“…Before clinical applications, more information is needed regarding the behaviour of stents implanted in human atherosclerotic arteries. In this context, Voisard et al [15]have reported a human organ culture model using renal atherosclerotic arteries injured by balloon angioplasty. Their 2-month study provides valid information on the healing process in humans.…”

Section: Introductionmentioning

confidence: 99%

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Neointimal Hyperplasia after Stenting in a Human Mammary Artery Organ Culture

Guérin

Rondeau²,

Grimandi³

et al. 2004

J Vasc Res

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Although the use of stents has limited the incidence of restenosis, in-stent restenosis remains an important problem. In-stent restenosis is the result of a healing process that induced neointimal hyperplasia through mechanisms that are still not understood. The aim of this study was to analyze the histological consequences of the healing process following stent implantation. Internal mammary arteries from atheroslerotic patients undergoing coronary artery bypass surgery were stented and maintained in culture for 0–28 days. Stent implantation after predilatation induced an extensive loss of endothelial cells whereas direct stenting preserved endothelium between the struts. Morphometric analysis shows that stent placement induced neointimal thickening. Smooth muscle α-actin labeling indicates that neo-intimal formation was mainly due to proliferation and migration of smooth muscle cells. Smooth muscle cell proliferation, assessed by MIB-1 staining, was maximal at day 14 after stent insertion. Human mammary artery organ culture thus provides valuable information on histological consequences of stent implantation with or without predilatation regarding endothelial cell disappearance and neointimal hyperplasia. These data also demonstrate that neointimal thickening induced by stent implantation comprises an intrinsic component resulting from the vessel wall response to stent insertion and suggest that blood factors could play an amplifying but not necessary role.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Neointimal Hyperplasia after Stenting in a Human Mammary Artery Organ Culture

Guérin

Rondeau²,

Grimandi³

et al. 2004

J Vasc Res

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“…Considerable attention has been given to the study of smooth muscle organ culture in an attempt to better understand smooth muscle gene regulation, response to growth factors, and regulation of proliferation (7,26). Cell and organ culture of VSM has been shown to change expression of both smooth muscle-specific and more ubiquitous genes potentially involved in modulation of these functions (21).…”

Section: Discussionmentioning

confidence: 99%

Effects of organ culture on arterial gene expression and hypoxic relaxation: role of the ryanodine receptor

Thorne

Rutgeerts

2003

American Journal of Physiology-Cell Physiology

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. Effects of organ culture on arterial gene expression and hypoxic relaxation: role of the ryanodine receptor. Am J Physiol Cell Physiol 284: C999-C1005, 2003. First published December 11, 2002 10.1152/ajpcell.00158.2002.-Organ culture specifically inhibits vasorelaxation to acute hypoxia and preferentially decreases specific voltage-dependent K ϩ channel expression over other K ϩ and Ca 2ϩ channel subtypes. To isolate further potential oxygen-sensing mechanisms correlated with altered gene expression, we performed differential display analysis on RNA isolated from control and cultured coronary arterial rings. We hypothesize that organ culture results in altered gene expression important for vascular smooth muscle contractility important to the mechanism of hypoxia-induced relaxation. Our results indicate a milieu of changes suggesting both up-and downregulation of several genes. The altered expression pattern of two positive clones was verified by Northern analysis. Subsequent screening of a porcine cDNA library indicated homology to the ryanodine receptor (RyR). RT-PCR using specific primers to the three subtypes of RyR shows an upregulation of RyR2 and RyR3 after organ culture. Additionally, the caffeine-and/or ryanodine-sensitive intracellular Ca 2ϩ store was significantly more responsive to caffeine activation after organ culture. Our data indicate that organ culture increases expression of specific RyR subtypes and inhibits hypoxic vasorelaxation. Importantly, ryanodine blunted hypoxic relaxation in control coronary arteries, suggesting that upregulated RyR might play a novel role in altered intracellular Ca 2ϩ handling during hypoxia. ryanodine receptor; vascular smooth muscle; hypoxia A DECREASE IN OXYGEN TENSION (PO 2 ), or hypoxia, modulates coronary, and most systemic, arterial tone, causing a vasodilation to maintain delivery of adequate oxygen to the heart and other organs. The mechanism(s) by which systemic vascular smooth muscle (VSM) senses these changes in PO 2 remains unclear. Common theories include the modulation of ion channel function, an acute decrease in available ATP necessary for force maintenance, direct regulation of intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ), and modulation of Ca 2ϩ sensitivity (6,8,9,19). We have shown that these theories cannot completely account for the hypoxiainduced relaxation of porcine coronary arteries (20).Additionally, considerable attention has been given to small heme-containing proteins as the oxygen sensor where an PO 2 -dependent change in redox status may transduce the appropriate response (12,14,15).In a recent investigation, we demonstrate the specific inhibition of relaxation to acute hypoxia after organ culture of porcine coronary arteries (25). Organ culture of VSM is reported to cause changes in [Ca 2ϩ ] i handling (4, 7) and has been associated with altered gene expression (21). Chronic hypoxia leads to the regulation of several hypoxia-inducible genes that modulate long-term responses to decreases in PO 2 (1,13,22). It is conceiva...

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“…These results suggest that chronic FBS-treatment of rabbit mesenteric arteries impairs muscle contractility by inducing the morphological and phenotypic changes in smooth muscle cells. Voisard et al (8), on the other hand, explored the organ culture with FBS for experimental models of restenosis. After the treatment of renal arteries with FBS for up to 3 weeks, bromodeoxyuridine (BrdU)-positive cells were detected in the neointima, indicating mitotic activity in this area.…”

Section: -2 Fetal Bovine Serummentioning

confidence: 99%

Organ Culture as a Useful Method for Studying the Biology of Blood Vessels and Other Smooth Muscle Tissues

Ozaki

Karaki

2002

Japanese Journal of Pharmacology

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ABSTRACT-The benefit of organ culture is to retain the original structural relationship between various cell species and their interactions and enable us to study the long-term effects of exogenous stimuli. Organ culture methods have been used especially in the studies of the proliferative vascular diseases, such as atherosclerosis and restenosis. We describe here that organ culture is a useful in vitro method to study the biology of vascular and other smooth muscle organs.

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A human arterial organ culture model of postangioplasty restenosis: results up to 56 days after ballooning

Cited by 24 publications

References 49 publications

Neointimal Hyperplasia after Stenting in a Human Mammary Artery Organ Culture

Neointimal Hyperplasia after Stenting in a Human Mammary Artery Organ Culture

Effects of organ culture on arterial gene expression and hypoxic relaxation: role of the ryanodine receptor

Organ Culture as a Useful Method for Studying the Biology of Blood Vessels and Other Smooth Muscle Tissues

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