PubMed Health⌕ Search

Biomedical subjects

E Betz

Publications and source records attributed to E Betz.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of cellular proliferation after experimental balloon angioplasty by low-molecular-weight heparin.

BACKGROUND: The proliferative response induced by balloon angioplasty is known to be an important factor in the development of restenosis after successful coronary angioplasty. METHODS AND RESULTS: To study the effects of low-molecular-weight heparin (LMWH) on cellular proliferation after experimental balloon angioplasty, LMWH (3.9 kd, 400 anti-Xa units/kg/day) was given to 20 male New Zealand White rabbits. After an intimal fibromuscular plaque was induced by electrical stimulation in the right carotid artery, LMWH was applied during the 7 days after balloon dilatation. As the control group, 20 other rabbits underwent balloon angioplasty without application of LMWH. The vessels were excised 3, 7, 14, and 28 days after balloon treatment. During the final 18 hours before the rabbits were killed, bromodeoxyuridine was applied. Intimal wall thickness increased from 13 +/- 5 cell layers (preangioplasty control group) to 20 +/- 6 cell layers in the LMWH-treated group at 28 days (p less than 0.05). In contrast, histological examination of control animals 28 days after angioplasty revealed a significant increase to 35 +/- 15 cell layers (p less than 0.01). Immunohistological quantification showed a significant increase (p less than 0.001) of cells undergoing DNA synthesis at 3 (10.2 +/- 4.2%) and 7 (7.7 +/- 4.8%) days after balloon dilatation in control animals. In contrast, at 3 and 7 days after balloon treatment, the percentage of cells undergoing DNA synthesis in LMWH-treated rabbits was lower (3 days, 2.7 +/- 1.8%; 7 days, 1.9 +/- 0.3%) than the corresponding untreated controls but showed a significant increase (p less than 0.01) compared with the preangioplasty controls. The differences between the two groups were statistically significant, however (3 days, p less than 0.01; 7 days, p less than 0.05). As early as 14 days after angioplasty, the extent of cellular proliferation was normalized and was comparable to the preintervention levels in both groups. CONCLUSIONS: Our data indicate that the proliferative response after balloon angioplasty can be reduced in vivo by early treatment with LMWH and thus encourage further clinical investigations.

Angioplasty, Balloon↗
PubMed1992

Vascular injury and time course of smooth muscle cell proliferation after experimental holmium laser angioplasty.

BACKGROUND: In vitro experiments have shown that holmium laser energy can effectively ablate even calcified plaque in human arterial vessels. Because high-energy densities from holmium lasers can easily be transmitted through quartz fibers, this solid-state laser has been suggested as an alternative intraluminal treatment of atherosclerotic plaque. METHODS AND RESULTS: To develop an intimal plaque, 35 New Zealand White rabbits underwent electrical stimulation of their right carotid artery for 28 days. Subsequently, in 25 rabbits, holmium laser angioplasty (wavelength, 2.12 microns; pulse duration, 150 microseconds; energy density, 350 mJ/mm2) was performed. To study the morphological results, the vessels were excised after 7, 14, 28, and 42 days. Cross sections were analyzed in regard to laser-specific injury. Staining of alpha-actin was used to identify smooth muscle cells (SMCs). After bromodeoxyuridine labeling, the extent of proliferation (number of cells undergoing DNA synthesis) was determined by using a monoclonal antibody. Holmium laser ablation resulted in an initial decrease of the numbers of intimal cell layers in the early group (7 days after treatment: 5 +/- 1 cell layers with 76 +/- 39 microns; control: 13 +/- 3 cell layers with 144 +/- 44 microns). Quantification of SMCs undergoing DNA synthesis in the intima (control: 51 +/- 19 cells/mm2) showed a significant increase of labeled cells after 7 (216 +/- 74 cells/mm2, p = 0.003) and 14 days (281 +/- 139 cells/mm2, p = 0.011). Integrity of the internal elastic lamina was disrupted in all animals after intervention. Seven and 14 days after treatment, a considerable reduction of medial cell nuclei was found in 10 of 12 animals. SMC proliferation in the medial layer was increased within the first 2 weeks after laser ablation (168 +/- 113 cells/mm2; control: 8 +/- 4 cells/mm2; p = 0.023). Six weeks after holmium laser angioplasty, SMC proliferation had returned to control levels in the intima and remained increased in the medial layer. This proliferative response resulted in a significant increase of intimal thickening within 6 weeks after laser ablation (30 +/- 6 cell layers, 375 +/- 97 microns resp.; p = 0.001 each). CONCLUSIONS: Holmium laser treatment leads to considerable vessel wall injury and results in SMC proliferation in the intimal and medial layer with a maximum of proliferative activity within the first 2 weeks. Subsequently, this results in considerable intimal and medial hyperplasia within 6 weeks after treatment.

Angioplasty, Laser↗
PubMed1991

Proliferation of smooth muscle cells in the inner and outer layers of the tunica media of arteries: an in vitro study.

During the development of atherosclerotic and fibromuscular proliferates/lesions, smooth muscle cells (SMC) in the media, particularly near the lumen, are activated to migrate into the intima, where they continue to proliferate to form an intimal thickening. It is to date unclear whether SMCs situated adjacent to the adventitia possess a lower capacity to proliferate because they are a special subpopulation of medial SMCs or because the adventitia excerts an inhibitory effect. We have, therefore, developed an in vitro system whereby we have attempted to clear up this uncertainty. The following observations were made from the in vitro experiments: Media-explants from rabbit aorta were laid on a polycarbonate filter with pores 5 microns in diameter. The SMCs migrated through the pores and formed a fibromuscular proliferate on the other side of the filter. Endothelial cells were seeded on one side of the filter before media-explants were laid on the other side of the filter. The confluent endothelium inhibited migration of SMCs through the filter pores. Media-explants were placed between two polycarbonate filters (pores 5 microns diameter). In this "sandwich" arrangement SMCs migrated through both filters, i.e., in both directions. The quantity of migrating and proliferating cells through both filters was almost identical. This suggests that there is no difference in the migratory and proliferative capacity of SMCs in the inner and outer layers in the media of arteries. To investigate the influence of the adventitia on medial SMCs, media-explants were placed between a lower (5 microns) and an upper (0.2 micron) filter. On the 0.2 micron filter adventitia-explants were laid above the media-explants. The 0.2 micron filter prevented migration of SMCs from the media-explant into the adventitia and migration of fibroblasts from the adventitia into the media. Interestingly, the adventitial tissue inhibited proliferation of SMCs at the abluminal and migration and proliferation at the luminal side of the media-explant; the number of cells migrating through the 5 microns pores at the luminal side was diminished, suggesting that the adventitial tissue has an antiproliferative influence on SMCs. Moreover, it was found that in media-explants near the filter with adventitia, the medial SMCs were in a better preserved condition than at the de-endothelialised luminal side. As a control, cultures consisting of media-explants were incubated without filters (i.e., explant organ cultures). The proliferates in the concavity (luminal side) exhibited a pattern of proliferating SMCs different from that of the cells at the abluminal convexity.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMed1991

Fibromuscular proliferates induced in vitro using a trans-filter culture system.

A trans-filter co-culture system of vascular smooth muscle cells (SMC) and endothelial cells (EC) is compared with a trans-filter culture of SMC without EC. Explants from the tunica media of rabbit aorta are cultured on one side of a polycarbonate filter with a defined pore size (5 microns). Smooth muscle cells grow out from the media explants and migrate through the filter pores to the other side of the filter, where they proliferate. After 14 days in trans-filter culture, a multilayer resembling "fibromuscular plaques" seen in vivo is formed on the opposite side of the filter. Moreover, the proliferation rate of SMC that have migrated through the filter pores is demonstrated to be similar to that of SMC in intimal lesions induced by balloon catheter injury. In the trans-filter co-culture, a monolayer of endothelial cells (porcine, bovine, or human) is cultivated on one side of the filter. Media explants are placed on the other side. This arrangement mimics the in vivo situation of an arterial vessel wall with endothelium and media separated by a porous lamina. In this co-culture system, the few smooth muscle cells that migrate into the subendothelial space do not form a cell multilayer. A confluent endothelial cell layer is capable of inhibiting the formation of a proliferate in this co-culture system.

Animals↗
PubMed1991

Morphological changes and smooth muscle cell proliferation after experimental excimer laser treatment.

BACKGROUND: Little is known about the mechanism(s) in the development of restenosis after excimer laser angioplasty. Thus, the rationale of this study was to determine the time course of intimal and medial smooth muscle cell (SMC) proliferation and histomorphological changes after experimental excimer laser treatment. METHODS AND RESULTS: Laser ablation was performed in the right carotid artery of 34 New Zealand White rabbits after development of a fibromuscular plaque by repeated weak electrical stimulations. The vessels were excised 3, 7, 14, 21, 28, and 42 days after excimer laser treatment. Staining of alpha-actin was used to identify SMCs. In five rabbits (15%), a stenosis of more than 50% of luminal area was due to intimal proliferation of SMCs, and in four other rabbits, a total occlusion was due to organized thrombi. After the initial ablation of the performed plaque (13 +/- 6 intimal SMC layers) a continuous increase of intimal wall thickness was found from 7 +/- 6 SMC layers at 7 days to 28 +/- 5 intimal SMC layers at 28 days after excimer laser ablation (p less than 0.01). After 42 days, no additional increase of intimal thickening occurred. After bromodeoxyuridine labeling, the extent of cell proliferation (percent of cells undergoing DNA synthesis) in the intima and media was determined using a monoclonal antibody against bromodeoxyuridine. Immunohistological quantification of SMC proliferation in the intima revealed a significant increase of cells undergoing DNA synthesis at 3 (p less than 0.05) and 14 (p less than 0.01) days after laser treatment. Medial proliferation of SMCs was delayed and had a significant increase 7 days (p less than 0.05) after intervention. Twenty-one days after laser treatment, SMC proliferation in the intima as well as in the media was normalized. CONCLUSIONS: The proliferative response of SMCs after experimental excimer laser treatment will occur as a dynamic process with a maximum of SMCs undergoing DNA synthesis during 14 days after laser ablation, resulting in an increase of intimal thickening within 4 weeks after laser treatment. The extent of intimal hyperplasia due to SMC proliferation after excimer laser treatment is comparable with the effect of transluminal balloon angioplasty in this experimental model.

Angioplasty, Laser↗
PubMed1991

Human endothelial cells are stimulated and vascular smooth muscle cells are inhibited in their proliferation and migration by heparins.

The actions of two natural heparins and a semi synthetic low molecular weight heparin with low anticoagulant activity have been studied on the migration and proliferation of human vascular endothelial and vascular smooth muscle cells in vitro. In a migration assay non irradiated confluent cultures of endothelial cells and smooth muscle cells were "wounded" with a sharp razor blade in such a way, that the migration of individual cells from the wound edge into a region void of cells could be measured. The maximum distance migrated (perpendicularly to the wound edge) three days after wounding, was taken as an index for migratory activity. All tested heparins reduced migration of vascular smooth muscle cells and enhanced migration of vascular endothelial cells in a concentration dependent manner. Cell proliferation was studied in clone culture. All heparins tested were found to inhibit smooth muscle cell growth. The number of clones, as well as the size of single clones, were smaller with increasing concentrations of natural and low molecular weight heparin. The endothelial cells, however, exhibited contrary responses; with increasing concentrations of heparin, the cloning efficiency and the cell number of individual endothelial cell clones increased. This opposite effects of natural heparins and low molecular weight heparin could be of importance in preventing secondary stenosing intimal proliferations after angioplasty, bypass operation and embolectomy or even atherogenesis. Since the low molecular weight heparin has only a low anticoagulatory activity, it may be more appropriate than natural heparins for long term therapy to prevent artery stenoses caused by intimal SMC proliferation.

Cell Division↗
PubMed1991

Calcium antagonists and atherosclerosis.

Numerous trials have used calcium antagonistic substances to inhibit or prevent genesis and progression of atherosclerosis, as well as disintegration of intimal proliferates and calcium deposition in atheromas or in matrix tissue of artery walls. In experimental models, various components involved in the development of atherosclerosis can be influenced by calcium antagonists. Transendothelial transport through interendothelial spaces and through the endothelial cells are sensitive to calcium antagonists of various types. Some drugs with calcium antagonistic properties are capable of inhibiting the development of stenosing proliferates caused by ballooning or other types of local artery wall stimulation. With cultures of cells obtained from normal and atherosclerotic arteries, insights into the mechanisms are possible by which various calcium antagonists influence the development and the progression of atherosclerosis.

Animals↗
PubMed1991

[Arteriosclerosis research in the animal model and cell cultures].

Feeding animals a diet of increased cholesterol content gave rise to the feeding hypothesis, and balloon experiments were the basis of the injury hypothesis of atherogenesis. When analyzing the sequence of events in arterial walls during atherogenesis, it turned out that in spite of complex causes and courses of stenosing processes in arterial walls the final results were relatively uniform: atheromas of fibromuscular proliferates or a mixture of both develop. Calcification of the thickenings of arterial walls occurs frequently in the progression of the disease. In animal experiments, the development of arteriosclerosis can be speeded up with various experimental techniques and enables study of the action of drugs to inhibit atherogenesis, as well as therapies for restenoses which frequently occur after angioplasty or bypass operations. In studies of drug effects the limitations of animal experiments become obvious when trying to transfer results obtained in animal experiments to the situation in humans. Cultures of cells from human arteries are, therefore, necessary supplements. Mass cultures and clone cultures of arterial walls are, however, very artificial systems. Therefore, co-cultures of endothelial cells, smooth muscle cells, and adventitial tissue have been established which imitate the morphology of arterial walls. With transfilter co-cultures, it has become possible to produce fibromuscular proliferates in vitro. When oxidized LDL-particles and monocytes are added to the culture medium, lipid-containing proliferates develop.

Animals↗
PubMed1991

[Effect of dihematoporphyrin derivatives on cultivated human smooth muscle cells from normal and atherosclerotic vascular segments-- Overview of results and implications for photodynamic therapy].

It is little known that photosensitizing porphyrins can be used not only for the localization and photodynamic therapy of tumors, but that they also accumulate in atherosclerotic plaques. This observation might be of interest for the detection and therapy of vascular stenoses. The present study examines whether dihematoporphyrin-ester and -ether, at clinically relevant concentrations, selectively influence cultured smooth muscle cells from human atherosclerotic plaques (primary stenoses and secondary stenoses) in comparison to smooth muscle cells obtained from non-atherosclerotic arteries. The results demonstrate that the drug accumulated to a greater extent in plaque-derived cells than in smooth muscle cells from normal arteries. Even without photoactivation, dihematoporphyrin-ester and -ether significantly decreased the proliferative activity of cells from atherosclerotic plaques. Light exposure of porphyrin-labeled cells resulted in a more pronounced sensitivity of plaque cells when compared with smooth muscle cells from non-atherosclerotic arterial wall. A comparison of the proliferative activity of cells before and after photodynamic reaction demonstrated that this activity was unaltered in surviving smooth muscle cells from non-atherosclerotic arteries, whereas surviving plaque-derived cells exhibited a significantly decreased or even non-proliferative activity. From the in vitro studies, a porphyrin concentration of 1-5 micrograms/ml (= 1-5 mg/kg body weight in vivo after systemic application) seems to be the most suitable dosage. In addition, morphological alterations of the cells caused by photodynamic reaction were documented.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Restenosed growth of plaque cells from restenosed peripheral and coronary plaque material of the human in vitro: a correlation to animal experiment results following angioplasty].

In this study cells were isolated from primary-stenosing and re-stenosing tissue of human peripheral (extraction by Prof. Höfling and Dr. Bauriedel, Munich) and coronary arteries. The vast majority of plaque cells was identified as smooth muscle cells (SMC) by positive reaction with monoclonal antibodies against smooth muscle alpha-Actin. All SMC consisted of two different subpopulations, which were discriminated by different cell diameters: Relatively small cells (diameter: 18.0 +/- 4 microns, mean +/- SD) and large cells (diameter: 26.0 +/- 3 microms, mean +/- SD). Population doublings per day (PD/day) for SMC from re-stenosing lesions were significantly increased (0.60 +/- 0.13 PD/day, mean +/- SD) in comparison to SMC from primary-stenosing lesions (0.15 +/- 0.04 PD/day, mean +/- SD), p much less than 0.001). Thus, the increased growth of SMC from restenosing lesions in vitro might be the equivalent to the rapid progression of restenosing events after angioplasty in vivo. These results are in accordance with data from experimental studies after angioplasty.

Aged↗
PubMed1991

The CARDIA dietary history: development, implementation, and evaluation.

To meet the objectives for dietary assessment in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective study, we developed a dietary history to provide accurate and reliable quantitative data on habitual individual nutrient intakes at baseline. The CARDIA dietary history was an interviewer-administered method that included a short questionnaire regarding general dietary practices followed by a comprehensive food frequency questionnaire about typical intake of foods using the previous month as a reference for recall. For each broad category of foods, participants were questioned in detail about specific foods only if they indicated that they consumed foods from that category. Follow-up questions for selected foods concerned serving size, frequency of consumption, and common additions to these foods. Provision was made for reporting foods not found in the food frequency list. The interview took approximately 45 minutes. Cue cards prompted responses and plastic food models assisted in estimating usual amounts consumed. A precoded format standardized coding for reported items and established the detail needed for recall during the interview. Baseline nutrient analyses from the CARDIA dietary history provided estimates that agreed reasonably well with expected caloric intake for body mass index according to the age- and sex-specific Recommended Dietary Allowances, but were higher than those reported from 24-hour recalls for comparable age, sex, and race groups in the second National Health and Nutrition Examination Survey. The CARDIA dietary history is a comprehensive assessment tool that can provide a dietitian with detailed information regarding habitual eating patterns and nutrient intakes among adults.

Adult↗
PubMed1991

[Transluminal excimer laser angioplasty of experimentally-induced atheromatous plaque: morphologic changes and importance of proliferation of smooth muscle cells].

To determine the time-course of morphological changes after excimer laser treatment of atherosclerotic carotid arteries, laser angioplasty was performed in 34 rabbits after production of an intimal plaque (13 +/- 6 cell layers, 30 +/- 9% stenosis) using electrical stimulations. The animals were sacrificed 3, 7, 14, 21, 28, and 42 days after laser treatment. A total or subtotal thrombotic occlusion was found in four cases. No perforation was observed, but in 10 animals histological examination evidenced a partial ablation of the medial layer with signs of local thrombus formation and local reduction of SMC in the media. In five animals a stenosis of more than 50% of luminal reduction was due to intimal proliferation of smooth muscle cells (SMC), as determined by a monoclonal antibody against alpha-actin. After the initial ablation, a continuous increase of intimal cell layers was found, from 7 +/- 6 cell layers (19 +/- 9% stenosis) at 7 days, to 28 +/- 5 cell layers (45 +/- 18% stenosis) at 28 days following excimer laser angioplasty (p less than 0.01). After 42 days no additional increase of intimal thickening occurred. Our data suggest that incidence and morphology is comparable to the proliferative response of SMC following conventional balloon angioplasty.

Angioplasty, Laser↗
PubMed1990

In vitro growth characteristics of human atherosclerotic plaque cells: comparison of cells from primary stenosing and restenosing lesions of peripheral and coronary arteries.

Cell size distribution and growth rates were studied in vitro in human plaque cells from advanced primary stenosing and fresh restenosing lesions of peripheral and coronary arteries. Cells were isolated either by the explant technique or by enzymatic disaggregation and were identified as smooth muscle cells by their typical growth pattern and their positive reaction with antibodies against smooth muscle alpha-actin. Endothelial cells were found in plaque specimens from coronary arteries but were only present in primary cultures. Smooth muscle cells from primary stenosing tissue (ps-SMC) exhibited a significantly lower growth rate in culture (0.15 +/- 0.04 population doublings per day; means +/- SD) compared with cells from restenosing lesions (re-SMC; 0.60 +/- 0.13 population doublings per day; means +/- SD). ps-SMC usually became senescent in their second passage, i.e., after 5-7 cumultive population doublings. re-SMC retained their high proliferative activity even after five passages (15 cumulative population doublings). Cell populations of both origins consisted of two distinct subpopulations which could be discriminated by cell size measurements: relatively small, predominant cells (cell diameter: 18.0 +/- 4 microns; means +/- SD) and large fibroblast-like cells (cell diameter: 26.0 +/- 3 microns; means +/- SD). The proportion of large cells was higher in cell populations derived from primary stenosing tissue. These results suggest that stenosing plaque tissue from human peripheral and coronary arteries consists of two smooth muscle cell subpopulations. The low proliferative activity of total smooth muscle cell populations of advanced primary stenosing lesions contrasts with the high mitotic activity of smooth muscle cells obtained from secondary stenosing intimal proliferates.

Aged↗
PubMed1990

Responses of cultured smooth muscle cells from human nonatherosclerotic arteries and primary stenosing lesions after photoradiation: implications for photodynamic therapy of vascular stenoses.

Cultured smooth muscle cells from human nonatherosclerotic arteries and from primary stenosing lesions were labeled with dihematoporphyrinester and ether, a photosensitizing probe used mainly for the detection and photodynamic therapy of tumors. After labeling for 24 h, cells were irradiated with ultraviolet light (wavelength 365 nm, energy densities ranging from 30 to 1,200 mJ/cm2). Twenty-four hours after photoradiation, 80% of smooth muscle cells from nonatherosclerotic arteries and only 20% of smooth muscle cells from atherosclerotic plaques were viable and still adherent. Moreover, dynamic cell and cytoskeletal alterations in response to irradiation are described. The differential sensitivity of smooth muscle cells from nonatherosclerotic arteries and from atherosclerotic plaques provides evidence that a photodynamic treatment might be a valuable therapeutic approach to vascular stenosis.

Arteriosclerosis↗
PubMed1990

Time course of smooth muscle cell proliferation in the intima and media of arteries following experimental angioplasty.

Smooth muscle cell (SMC) proliferation is known to be an important factor for the development of restenosis after percutaneous transluminal coronary angioplasty. To determine the time course of intimal and medial SMC proliferation and morphological changes after experimental angioplasty, an intimal atheroma was produced with repeated weak electrical stimulations in the right carotid artery of 45 male New Zealand White rabbits. Angioplasty was subsequently performed in 35 rabbits, and the proliferative responses were analyzed with histomorphological and immunohistological criteria at 3, 7, 14, 21, 28, and 42 days after intervention. A hemodynamic relevant stenosis after angioplasty was found in eight (23%) of 35 dilated arteries. In five rabbits the stenosis was due to a mural thrombus, and in three animals restenosis was caused by intimal SMC proliferation. In all dilated arteries the intimal wall thickness increased from 13 +/- 5 intimal cell layers (after electrical stimulation) to 33 +/- 14 cell layers during 28 days after angioplasty (p less than 0.05). Later than 4 weeks after angioplasty, no additional increase of intimal thickening occurred. Application of bromodeoxyuridine 18 and 12 hours before excision of the vessels allowed determination of the percent of cells undergoing DNA synthesis in the intima and media using monoclonal antibody against bromodeoxyuridine. SMCs were identified by alpha-actin staining. Immunohistological quantification of intimal SMC proliferation showed a maximum of cells undergoing DNA synthesis within the first 7 days after angioplasty (p less than 0.01). In contrast, medial proliferation of SMCs was delayed and showed a small but significant increase 21 days after dilatation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗