Effect on intimal hyperplasia of dexamethasone released from coated metal stents compared with non-coated stents in canine femoral arteries.

PURPOSE: Polymer-coated, dexamethasone (DXM)-releasing stents were tested in order to assess the efficacy of DXM released locally for the prevention of stent restenosis due to intimal hyperplasia. METHODS: Strecker stents coated with a biodegradable membrane containing DXM were implanted percutaneously into the femoral artery in 14 dogs. The contralateral artery received a conventional non-coated stent serving as control. The drugs are eluted by degradation of the carrier membrane. Follow-up intraarterial digital subtraction angiography (DSA) was obtained at 3, 6, 9, 12, and 24 weeks with subsequent autopsy. Specimens for gross and microscopic pathology were obtained and histomorphometry was performed. RESULTS: Four of 14 DXM-coated stents showed thrombotic occlusion within the first 3 weeks; ten DXM-coated stents remained patent. At follow-up DSA, DXM-coated stents showed a significantly wider lumen than the non-coated stents. At morphometry there was less intimal hyperplasia over DXM-coated stents than over non-coated stents (p < 0.05). CONCLUSION: DXM-coated stents reduce neointimal hyperplasia in dogs when compared with non-coated stents.

Smooth excimer laser coronary angioplasty (SELCA) and conventional excimer laser angioplasty: Comparison of vascular injury and smooth muscle cell proliferation.

Although the excimer laser, which utilizes 'non-thermal ablation effects', has achieved encouraging results in early clinical trials, the long-term results have failed to show any advantage over conventional percutaneous transluminal coronary angioplasty (PTCA).A new system, Smooth Excimer Laser Coronary Angioplasty (SELCA), has been developed to reduce the tissue damage in the vessel wall caused by shock waves and vapour bubbles.SELCA (wavelength 308 nm, pulse duration 115 ns, repetition rate 150 Hz and energy density 50 mJ mm(-2)) lowers the amount of shock wave formation and pressure peak amplitude in the surrounding tissue by about eight times when compared to the conventional 308 nm excimer laser (ELCA). In this preclinical evaluation, this new system was compared to ELCA. Fifty New Zealand White rabbits were stimulated by repeated weak DC impulses for a period of 28 days in order to form an atherosclerotic plaque in the right carotid artery. The vessels were excised 3, 7,14 and 28 days after laser irradiation for immunohistochemical analysis.SELCA and ELCA laser treatment lead to a decrease in maximal intimal wall thickness 3 days after intervention (control: 177+/-4 microm; SELCA: 131+/-22microm; ELCA: 120 +/-33microm). In the period between 3 and 28 days, a moderate increase in intimal wall thickness was observed after SELCA treatment compared to a significant increase after ELCA (28 days after intervention: SELCA: 157+/-22microm; ELCA: 274 +/-28microm). Bromodeoxyuridine (BrdU) was applied 18 and 12 h before excision of the vessels in order to determine the percent of cells undergoing DNA synthesis. The percent of BrdU labelled SMC in the intima (control: 13 +/- 2 cells mm(-2)) increased in both groups after 3 days (SELCA: 248 +/- 107 cells mm(-2); ELCA: 162 +/- 41 cells mm(-2)) and 7 days (SELCA: 162+/- 55 cells mm(-2); ELCA: 279 +/- 119 cells mm(-2)).The present results demonstrate that vascular wall injury and increase in intimal wall thickness following SELCA are reduced in comparison to the results achieved with the conventional technique. Further trials are necessary to assess whether these improvements will lead to more favourable long-term results after excimer laser angioplasty.

Induction of cell-rich and lipid-rich plaques in a transfilter coculture system with human vascular cells.

Cell-to-cell interactions are mainly involved in the control of the proliferation, migration, differentiation and function of different cell types in a wide range of tissues. In the arterial vessel wall, human arterial endothelial cells (haEC) and smooth muscle cells (haSMC) coexist in close contact with each other. In atherogenesis, haSMC can migrate from the media to the subintimal space to form fibromuscular and atheromatous plaques. In the present study, a transfilter coculture system is described, in which the interface between haSMC and confluent or proliferative haEC can be studied in detail. Cells were cocultured on the opposite sides of a porous filter which separates both cell types like the internal elastic lamina in vivo. In cocultures containing proliferative haEC, haSMC growth was significantly stimulated (33.4 +/- 5.7 cells/section, p < 0.05) compared to haSMC monocultures (22.9 +/- 2.5 cells/section) and cocultures containing confluent haEC (15.6 +/- 2.9 cells/section). If confluent haEC were injured mechanically, haSMC growth increased highly significantly (71.3 +/- 16.8 cells/section, p < 0.001). Thus, cell-rich proliferates containing 5-7 layers of haSMC embedded in extracellular matrix were formed after 14 days. On the other hand, after haSMC migration to the endothelial side had occurred, the addition of LDL and monocytes to cocultures with arterial media explants and haEC resulted in the formation of lipid-rich, low-cellular structures. After 28 days, characteristic in vitro plaque growth was induced; the plaque contained a lipid core with predominantly necrotic cells, extracellular lipid accumulations, atypically shaped lipid-loaded haSMC and macrophages, similar to in vivo foam cells, as well as an increased amount of extracellular matrix (collagen I, III and IV). These areas were surrounded by typical fibromuscular caps consisting of smooth muscle alpha-actin-positive haSMC. Finally, the formation of capillaries by haEC could also be observed within these structures.

Covered stents for prevention of restenosis. Experimental and clinical results with different stent designs.

RATIONALE AND OBJECTIVES: Metallic stents in small vessels go along with a significant risk of restenosis and reocclusion. Different models of stents and covering materials have been purported to prevent intraluminal neointimal proliferation by cover-based closure of the spaces in the wire mesh. METHODS: Tantalum stents covered with polyethylacrylate/polymethylmethacrylate (PEM) were implanted in the infrarenal aorta of six New Zealand white rabbits by aortotomy and compared with eight rabbits treated with uncovered tantalum stents. For deployment, covered and uncovered stents necessitated a 7-French (F) and 5-F sheath, respectively. In addition, nine human patients with arteriosclerotic lesions of the superficial femoral arteries (stenosis > 5 cm or total occlusion) were treated percutaneously with a Dacron-covered nitinol vascular stent via a 9-F sheath. Patients were followed for a mean of 13.5 months, and control angiography was performed after 6 months. RESULTS: Experimental placement of the tantalum Wiktor stent was feasible technically in all cases. Five of six stents covered with PEM were occluded 3 days after placement despite the intravenous use of heparin and aspirin. In the group with uncovered stents, no area of stenosis greater than 10% was observed. There was a neointimal layer of 89 +/- 68 microns around the stent wires. Stent placement was successful in all patients. In four patients, a hyperergic reaction occurred, resulting in noninfectious periarteriitis. This complication was treated successfully with nonsteroidal antiinflammatory drugs. The primary patency was 50%, and the secondary patency (after application of a second covered stent in two patients) was 63%. CONCLUSIONS: The uncovered stent induces little neointimal proliferation around the stent wires. The insertion of stents covered with PEM into the rabbit aorta was accompanied by a strong thrombotic reaction, despite sufficient anticoagulation. Dacron-covered nitinol stents showed a surprisingly high restenosis rate after 9 months of follow-up. Further research concerning the in vivo properties of new covering materials is mandatory before routine vascular clinical application.

Lifestyle intervention: results of the Treatment of Mild Hypertension Study (TOMHS).

BACKGROUND: Questions regarding the efficacy of nonpharmacologic approaches for the treatment of stage 1 hypertension were addressed as part of the Treatment of Mild Hypertension Study (TOMHS), a 4-year, randomized clinical trial (N = 902). This report describes the lifestyle intervention program used in TOMHS, presents data on the lifestyle changes observed, and focuses on the effect of weight loss on blood pressure and blood lipid levels. METHODS: Participants were randomly assigned to receive either placebo or one of five different antihypertensive medications. All took part in a lifestyle intervention program to reduce weight and sodium and alcohol intake and to increase physical activity. RESULTS: Substantial changes from baseline levels were achieved for all lifestyle intervention variables. Mean weight change was -10.5 lb (-5.6%) at 1 year, -8.5 lb (-4.5%) at 2 years, -7.4 lb (-4.0%) at 3 years, and -5.7 lb (-3.0%) at 4 years. At 4 years, 70% of participants remained below baseline weight and 34% maintained a weight loss of 10 lb or greater. Mean change in urinary sodium excretion was -12.5 mmol/8 hr (-23%) at 1 year, -10.7 mmol/8 hr (-20%) at 2 years, -8.4 mmol/8 hr (-16%) at 3 years, and -4.6 mmol/8 hr (-9%) at 4 years. Alcohol intake declined by 1.6 drinks/week among drinkers at 4 years. Reported leisure physical activity increased by 86% at 1 year and remained 50% above baseline at 4 years. Beneficial changes in blood pressure and serum lipids were associated with these changes. CONCLUSIONS: These results support a role for lifestyle interventions as the initial treatment for stage 1 hypertension and demonstrate that such interventions can be successfully implemented in the clinical setting.

Prolonged proliferative response of smooth muscle cells after experimental intravascular stenting.

The purpose of this experimental in vivo study was to determine the time course of smooth muscle cell proliferation early and late after intravascular stenting compared to conventional balloon angioplasty in normal vessels. A balloon expandable 2.0 mm tantalum Strecker stent was placed in the right carotid artery of 33 male New Zealand White rabbits after they had been fed a 0.5% cholesterol diet for 28 days. In addition, balloon angioplasty was performed in 27 of the animals; 19 contralateral vessels served as controls without treatment. The vessels were excised at 7, 14, 28, 42 or 90 days after treatment. During the final 18 h before the rabbits were killed, bromodeoxyuridine (BrdU) was applied and proliferating cells were detected by using a monoclonal antibody against BrdU. In histological cross sections the proportion of cells undergoing DNA synthesis was determined. Analysis was performed separately in the intimal and medial layers. Additionally, the area adjacent to the stent wire was compared with the intermediate area. Smooth muscle cells were identified by alpha-actin staining. Intimal wall thickness increased from 23 +/- 28 microns (control group without intervention) to 323 +/- 84 microns within 42 days after stenting (P < 0.01), and to 81 +/- 82 microns at day 42 after balloon angioplasty (P < 0.05). However, between 42 and 90 days following stent implantation a significant (P < 0.05) decrease in neointimal thickness was observed (90 days: 215 +/- 15 microns).(ABSTRACT TRUNCATED AT 250 WORDS)

Current status of the Strecker stent.

Knitted flexible tantalum stents proved to be a valuable adjunct to percutaneous transluminal angiplasty (PTA) in the case of insufficient PTA results, and their use was established in the distal aorta, the iliac, the femoro-popliteal, the renal, and the coronary arteries. Recently, long arterial occlusions were defined as new indications for primary stenting; stent indications were further extended to the subclavian, the carotid, and the splanchnic arteries. Due to higher incidence of acute and late complications after stent treatment of small diameter arteries, patients have to be selected thoroughly. Newly designed drug-releasing stents tested in animal experiments promised to be suitable to diminish the incidence of late restenosis due to intinal hyperplasia, thus providing better long-term patency.

Effects of dietary garlic supplementation in a rat model of atherosclerosis.

In the present study possible antiatherogenic effects of dietary garlic were investigated in an experimental model which consists in the deendothelialisation by ballooning of the a. carotis communis of rats. 3 experimental groups were established: group I received a standard diet; the diet of group II was supplemented with 2% cholesterol and group III received 2% cholesterol and 5% dried garlic powder. Four weeks after ballooning plasma cholesterol, the average thickness of the neointima as well as the DNA content and the expression of collagens type I, III and IV in the ballooned arterial segment were determined. Furthermore, the specific activities of the enzymes glutathione peroxidase, glutathione disulfide reductase, glutathione-S-transferase and glucose 6 phosphate dehydrogenase were measured in homogenates of liver, heart and aorta. Hypercholesterolemia induced by cholesterol-feeding (group II 92 +/- 18 mg/100 ml) was significantly reduced by garlic (group III 53 +/- 19 mg/100 ml). Only little effects of garlic were seen in inhibiting neointima after ballooning. However, significant effects were found in protecting the enzymes of the glutathione dependent peroxide detoxification system, which is strongly impaired under hypercholesterolemia. Generally a normalisation, in some cases even an improvement beyond that, of the enzyme activities occurred in the garlic treated group. This indicates that in the model of atherosclerosis used here garlic is effective in lowering plasma cholesterol and in improving peroxide detoxification, however, it has only little influence on the wound healing reaction and does not significantly inhibit the development of intimal thickenings after ballooning.

Recruitment and dynamics of leukocytes in the formation of arterial intimal thickening--a comparative study with normo- and hypercholesterolemic rabbits.

Leukocyte involvement in intimal thickening was investigated as a function of time and diet. Fibromuscular or foam cell-rich thickings were induced by electrical stimulation (ES) of carotid arteries in rabbits either on a normal or a high (1%) cholesterol diet. Under both dietary conditions granulocytes (predominantly neutrophils), monocytes and lymphocytes migrated through and accumulated beneath a continuous, yet structurally altered endothelium already after 1 day of ES. This preceded the occurrence of smooth muscle cells (SMCs) in the intima. Under normocholesterolemia, leukocyte attachment to the endothelium decreased with continued ES, which coincided with the re-establishment of a normal endothelial cell pattern. Neutrophils ceased to invade the stimulated intima and disappeared from the lesion after 14 days. The proportion of mononuclear leukocytes was also reduced in the thickened intima, finally amounting to 5.5 +/- 5.9% in the 4-week-old fibromuscular lesion where SMCs prevailed. Hypercholesterolemia did not affect neutrophil involvement in response to ES. However, it provoked lipid deposition first in macrophages, then in SMCs and resulted in elevated amounts of mononuclear leukocytes both within the foam cell-rich thickening and in association with the overlying endothelium. These data indicate adaptive behavior of leukocytic infiltration in the development of fibromuscular thickening, and a shift to a chronic inflammatory response under additional hypercholesterolemia.

In vitro model of the inner parts of a vessel wall with cultured human vascular cells.

BACKGROUND: Transfilter culture systems with enzymatically isolated human vascular cells were established to imitate the morphologic situation of the inner parts of a vessel wall. METHODS: In transfilter cultures, only smooth muscle cells were seeded on one side of the filter, whereas in transfilter cocultures, smooth muscle cells were cultivated in the presence of confluent or nonconfluent (injured) endothelial cells on the other side of the filter. The filter mimics the porous internal elastic lamina. Fourteen days after seeding, cultures were fixed, embedded in Araldite (Serva, Heidelberg, Germany), and prepared for histologic examination (light microscopy, indirect immunofluorescence staining of von Willebrand factor- and alpha-smooth muscle actin-antigen). RESULTS: In transfilter cultures, smooth muscle cells migrated through the pores to the opposite side of the filter, replicated there, and formed fibromuscular proliferates (two to four layers of smooth muscle cells). The proliferation rates of the smooth muscle cells were similar on both sides of the filter and showed an optimum rate on day 4 in culture as determined by 5-bromo-2'-deoxyuridine labeling. By cocultivating a confluent endothelial cell layer on one side of the filter, migratory activity of smooth muscle cells was inhibited. However, when smooth muscle cells were cultivated together with proliferating endothelial cells (injured state), proliferation of smooth muscle cells was massively stimulated (up to 12 layers of smooth muscle cells). CONCLUSIONS: The results indicate that the confluency of the endothelial cells and their proliferation rate influence the migratory and proliferative behavior of smooth muscle cells. The transfilter system may be a suitable model for prescreening of potential antiproliferative and antiarteriosclerotic drugs.

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.

Comparison of the cellular protein composition of aortic smooth muscle cells in vivo and in vitro by two-dimensional gel electrophoresis.

Vascular smooth muscle cells are of major interest for the evaluation of atherosclerotic processes. By the use of two-dimensional gel electrophoresis and subsequent silver staining we investigated the protein expression of smooth muscle cells in the native thoracic aorta, immediately after enzymatic disaggregation, in subconfluent proliferating and in postconfluent nonproliferating primary cell cultures. Compared to the native thoracic aorta the protein composition of smooth muscle cells in cell culture is changed dramatically. Furthermore, significant differences in protein expression between proliferating and nonproliferating smooth muscle cells in cell culture were found.

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.

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.

[Transluminal excimer laser angioplasty of experimentally-induced atheromatous plaque: morphologic changes and importance of proliferation of smooth muscle cells]. / Transluminale Excimer-Laserangioplastie von experimentell erzeugten atheromatösen Plaques: Morphologische Veränderungen und Bedeutung der Proliferation glatter Muskelzellen.

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.

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)