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Biomedical subjects

E Blessing

Publications and source records attributed to E Blessing.

18 recordsLinked to original sources
PubMed2005

A 6 week course of azithromycin treatment has no beneficial effect on atherosclerotic lesion development in apolipoprotein E-deficient mice chronically infected with Chlamydia pneumoniae.

OBJECTIVES: To evaluate whether antimicrobial chemotherapy prevents acceleration of atherosclerotic lesion development induced by infection with Chlamydia pneumoniae. METHODS: ApoE-deficient mice which develop hyperlipidaemia and atherosclerosis spontaneously were inoculated intranasally with C. pneumoniae. Animals were treated with azithromycin for 6 weeks after the third inoculation and the atherosclerotic lesion areas in the aortic sinus were measured by computer-assisted morphometry. RESULTS: At 12 weeks post-infection, infected untreated animals developed significantly larger lesion areas compared with sham-inoculated controls (8.7 x 10(4)+/-2.3 x 10(4) microm(2) versus 5.6 x 10(4)+/-2.4 x 10(4) microm(2)). However, there were no differences in lesion size of infected mice treated with azithromycin in comparison with untreated infected controls (11.0 x 10(4)+/-3.0 x 10(4) microm(2) versus 8.7 x 10(4)+/-2.3 x 10(4) microm(2)). CONCLUSIONS: Antibiotic treatment against C. pneumoniae has no beneficial effects on hyperlipidaemia-induced atherosclerosis accelerated by C. pneumoniae in a mouse model.

Animals↗
PubMed2002

Fibrinogen induces chemotactic activity in endothelial cells.

Chemotaxis of blood monocytes into the vessel wall together with the change of the relative content of the extracellular matrix (ECM) proteins at sites of predilection is an early cellular marker of atherogenesis. To examine the influence of ECM proteins on secretion of chemoattractants by endothelial cells (EC), porcine EC were seeded on gelatin (G), fibronectin (Fn) and fibrinogen (Fg). After 24 h cells seeded on G and Fn showed the histiotypic 'cobblestone'-morphology whereas cells seeded on Fg did not. Chemotactic activity for monocytes in supernatants from cells seeded on Fg was more than two-fold higher compared with G and was independent of soluble Fn or Fg in the supernatant. Quantification of monocyte chemoattracting protein-1, PDGF-AB and IL-8 in EC supernatants showed that Fg led to a significant increase in secretion of all three proteins compared with cells cultured on G. Preincubation of porcine EC with the tripeptide arginine-glycine-aspartic acid, as inhibitor of binding of Fg to integrin receptors, but not with the control tripeptide arginine-glycine-glutamic acid showed a decrease in chemotactic activity for cells cultured on Fg but not on Fn or G. Inhibition of protein kinase C (PKC) activity in EC by GF109203 resulted in a decrease of fibrinogen-induced chemotactic activity. Also the tyrosine-kinase inhibitor herbimycin inhibited fibrinogen mediated secretion of chemokines. The role of the PKC pathway for matrix mediated signal transduction is further corroborated by Fg-dependent induction of the PKC isoform delta. These data indicate an integrin-dependent signal transduction pathway leading to induction of chemotactic activity by the ECM protein fibrinogen. This mechanism may contribute to induction of chemokines in early atherosclerotic lesions.

Animals↗
PubMed2001

Phosphorylation of cytokeratin 8 and 18 in human vascular smooth muscle cells of atherosclerotic lesions and umbilical cord vessels.

Expression of cytokeratins (CK) is considered a hallmark of the state of epithelial differentiation. CK also occur in certain vascular smooth muscle cells (VSMC), inferring an association with a less differentiated phenotype. Recently, CK posttranslational modification was shown to occur in epithelial cells in stress, mitosis or apoptosis. The aim of this study was to determine potential CK phosphorylation patterns in human VSMC. Tissue samples of normal peripheral and coronary arteries, atherosclerotic lesions and umbilical cord vessels were evaluated by immunofluorescence microscopy applying antibodies specific for cytokeratins 8 and 18, specific cytokeratin phosphorylation sites, Ki-67-antigen as a proliferation marker and nick end labeling (TUNEL) to detect apoptosis. All samples contained cytokeratin-positive VSMC but diverse phosphorylation patterns. The C-terminal serine 431 of cytokeratin 8 (CK8Ser-431) was phosphorylated in the vast majority of CK-expressing VSMC of coronary artery lesions. Only a subset of these cells demonstrated phosphorylation of CK18Ser-33 or, to an even lesser extent, CK8Ser-73. DNA fragmentation occurred predominantly in samples containing cells with phosphorylated CK8Ser-431 domains. In contrast, occluded peripheral lesions exhibited little or no phosphorylation. Neonatal VSMC in umbilical cord vessels contain abundant phosphorylated CK domains, again predominantly CK8Ser-431, but also CK18Ser-33. Again, only single cells were found to be proliferating or to contain DNA fragmentation. Thus, abundant CK phosphorylation in VSMC of atherosclerotic lesions suggests a specific functional response to cell stress and a possible relation to apoptosis.

Aorta↗
PubMed2001

Chlamydia pneumoniae infection accelerates hyperlipidemia induced atherosclerotic lesion development in C57BL/6J mice.

Considerable evidence of an association between Chlamydia pneumoniae infections and cardiovascular disease has emerged. Animal models using genetically altered mice and hypercholesterolemic rabbits have shown a pathogenic role of C. pneumoniae in accelerating atherosclerotic plaque development. In the present study, we evaluated the effect of chronic C. pneumoniae infection on atherosclerosis in C57BL/6J mice, fed either a regular chow diet or a high fat, high cholesterol diet. Infected animals on an atherogenic diet developed significantly larger lesion areas compared with control mice at 18 weeks (2.5-fold increase; 4177+/-777 vs. 1650+/-808 microm(2); P<0.05) and 24 weeks of age (3.3-fold increase; 14139+/-4147 vs. 4298+/-869 microm(2); P<0.02). This study shows that chronic C. pneumoniae infection accelerates atherosclerotic lesion development in diet induced hypercholesterolemic mice, indicating that C. pneumoniae is a co-risk factor of hyperlipidemia in atherogenesis.

Animals↗
PubMed2000

Cardiac alpha-actin in smooth muscle cells: detection in umbilical cord vessels and in atherosclerotic lesions.

Phenotypic modulation of smooth muscle cells (SMC) is a key event during the development of atherosclerotic and restenotic lesions. During this process, the composition of the cytoskeleton is substantially altered, with changes predominantly in actin expression reflecting a shift from smooth muscle alpha-actin to the non-muscle beta-isoform. We now demonstrate that yet another actin isoform, cardiac alpha-actin, is synthesized, de novo, in SMC of various atherosclerotic lesions. Using a highly specific monoclonal antibody against cardiac alpha-actin, we analyzed and compared the accumulation of this actin isoform in diverse SMC by immunofluorescence microscopy and immunoblotting. As expected, cardiac alpha-actin was present in human myocardium but not in healthy SMC of adult aorta, coronary arteries, trabeculae of the spleen, colon, stomach or skeletal muscle. Interestingly, the presence of cardiac alpha-actin was detected in umbilical cord vessels, human myometrium, in atherosclerotic coronary lesions and atherosclerotic lesions from peripheral vascular disease. The distribution of cardiac alpha-actin often paralleled that of cytokeratins 8 and 18, intermediate filament proteins typically found in dedifferentiated SMC. Taken together, the data presented here illustrate the expression of cardiac alpha-actin to be limited to either fetal vessels or those vessels or tissue having suffered damage or atrophy, outside its 'native' environment in the heart. The demonstration of cardiac alpha-actin in SMC of umbilical cord vessels and in atherosclerotic lesions but not in apparently healthy vessels supports the notion that SMC in atherosclerotic lesions exhibit a dedifferentiated phenotype.

Actins↗
PubMed2000

Chlamydia, inflammation, and atherogenesis.

Atherosclerotic lesions are initiated and progress largely as a result of a chronic, fibroproliferative, inflammatory response. This review discusses how Chlamydia pneumoniae could conceivably contribute to this chronic inflammatory response and reports on recent in vivo and in vitro studies. In vivo studies in mice demonstrate that C. pneumoniae infection is disseminated to the artery wall following infection in the lung by alveolar macrophages. Recent in vitro studies show that infected U937 cells can directly transfer infection to endothelial cells and can indirectly increase the susceptibility of endothelial cells to C. pneumoniae infection. Loading of RAW 264.7 cells with modified forms of low-density lipoprotein increases the resistance of the cells to C. pneumoniae infection and also increases the susceptibility to the combined toxic effects of modified lipids and C. pneumoniae infection.

Animals↗
PubMed2000

Mouse models of C. pneumoniae infection and atherosclerosis.

Mouse models were used to determine whether Chlamydia pneumoniae establishes chronic infection of the aorta and contributes to atherogenesis. Persistent infection of the aorta occurred in 11 of 31 hyperlipidemic apolipoprotein E-deficient (apoE(-/-)) mice but not in C57BL/6J mice fed a normal diet after a single inoculation and in both models following repeated inoculation with C. pneumoniae. Repeated inoculation of C57BL/6J mice resulted in inflammatory changes in the heart and aorta in 8 of 40 of mice; however, no atherosclerotic lesion development was observed. Repeated inoculation of apoE(-/-) mice resulted in a statistically significant increase in lesion area (n=43; P=.05). Although Chlamydia trachomatis disseminated to the aorta, persistent infection was not established and no statistically significant increase in lesion area occurred. These studies suggest that persistent infection of the aorta can lead to inflammatory changes in the absence of hyperlipidemia and accelerate lesion progress in concert with hyperlipidemia.

Animals↗
PubMed2000

Effect of Chlamydia trachomatis infection on atherosclerosis in apolipoprotein E-deficient mice.

We have previously demonstrated that Chlamydia pneumoniae accelerates plaque formation in apolipoprotein E-deficient (ApoE(-/-)) mice following intranasal inoculations. In this study, we evaluated the effect of respiratory tract infection with Chlamydia trachomatis on the progression of atherosclerosis in ApoE(-/-) mice. The study showed that in contrast to infection with Chlamydia pneumoniae, infection of the lung and aorta with C. trachomatis was mild and transient and did not significantly accelerate plaque development.

Animals↗
PubMed2000

Chlamydia pneumoniae induces inflammatory changes in the heart and aorta of normocholesterolemic C57BL/6J mice.

Chlamydia pneumoniae infection induces inflammatory changes in blood vessels in normocholesterolemic rabbits, but it is not known whether the same phenomenon occurs in other animal models. Thus, in this study, C57BL/6J mice were inoculated with C. pneumoniae. Inflammatory changes in the heart or aorta were observed in a small number of chronically infected mice. No evidence of atherosclerotic lesions was found in any of the mice. These findings suggest that chronic C. pneumoniae infection can induce inflammatory changes in the heart and aorta of C57BL/6J mice, but does not initiate definitive atherosclerosis.

Animals↗
PubMed1999

Intravascular ultrasound and stent implantation: intraobserver and interobserver variability.

BACKGROUND: Intravascular ultrasound (IVUS) imaging can be used to optimize implantation of intracoronary stents; the variability of the measurements, however, remains unclear. Our aim in this study was to determine the intraobserver and interobserver variability of IVUS measurements after stent implantation. METHODS: Ninety-four patients underwent implantation of 100 Palmaz-Schatz stents in 98 lesions (79 de novo and 19 restenotic). IVUS measurements (3.5F, 30 MHz) of proximal and distal reference sections and of the smallest stent lumen were performed by 2 investigators. RESULTS: Intraobserver and interobserver correlations, respectively, were r = 0.96 and 0.93 for the proximal reference, r = 0.94 and 0.92 for the distal reference, and r = 0.97 and 0.97 for minimal stent lumen. Stent expansion (minimal lumen in the stent/mean reference area) showed a variability of r = 0.80 and 0.70. Taking a cutoff point of 90% for adequacy of stent expansion, observers agreed in only 77% whether the stent was adequately or inadequately expanded. CONCLUSIONS: IVUS enables reproducible lumen measurements in stents and reference sections. The degree of stent expansion, however, underlies a high measurement variability that can lead to different therapeutic strategies.

Coronary Disease↗
PubMed1999

Incomplete expansion of Palmaz-Schatz stents despite high-pressure implantation technique: impact on target lesion revascularization.

Improved expansion of stents using high-pressure implantation technique with subsequent antiplatelet therapy has improved patient outcome regarding the incidence of subacute stent thrombosis, bleeding complications and restenosis. Whether high-pressure implantation per se guarantees adequate stent expansion remains unclear. The aim of the study was to determine (1) stent expansion after high-pressure implantation technique and (2) whether stent expansion influences rate of target lesion revascularization within 6 months of follow-up. One hundred Palmaz-Schatz stents were implanted in 98 lesions (91 native vessels, 7 graft vessels) of 94 patients using high-pressure implantation technique (balloon pressure 12-20 atm). Stent expansion was investigated using intravascular ultrasound imaging (IVUS). Clinical follow-up of the patients was performed for 6 months. After implantation, stent/mean reference ratio was 0.81 +/- 0.16. Noncompliant balloons used for implantation were chosen by angiographic criteria. Mean balloon/reference ratio was 1.08 +/- 0.22; therefore balloons were not undersized. Additional balloon dilataion using higher pressures and/or larger balloons based on IVUS criteria and subsequent IVUS measurements was performed in 52 patients (55%); in these patients, stent expansion improved from 79 +/- 16 to 91 +/- 15% (mean +/- SD) of average reference areas (p < 0.002). Within the 6 months' clinical follow-up, target lesion revascularization was performed in 19 patients (20%). The only prognostic factors for the development of in-stent restenosis requiring target lesion revascularization were the vessel size (p < 0.05) and the extent of plaque distal to the stents (p < 0.05). Implantation of Palmaz-Schatz stents using high-pressure technique does not guarantee adequate stent expansion. Additional dilatation with higher pressures and/or larger balloons improves stent expansion. The size of the stented vessel and the extent of plaque at the distal stent end (residual outflow stenosis) but not the degree of stent expansion were predictors for target lesion revascularization within 6 months' follow-up.

Adult↗
PubMed1997

Efficacy of low-molecular-weight heparin delivery with the Dispatch catheter following balloon angioplasty in the rabbit iliac artery.

Local drug delivery can be achieved with active injection systems or passive contact of a compound with the arterial wall. The Dispatch catheter allows for passive diffusion of drugs from drug compartments while preserving blood flow through the central conduit. The aim of this study was to investigate whether a reduction in neointima formation can be achieved by local delivery of a limited amount of a highly concentrated solution of the low-molecular-weight heparin Reviparin. In 16 New Zealand white rabbits, successful balloon dilatation was performed in both iliac arteries, followed by local delivery of 4 ml Reviparin (1,000 IU/ml). The arteries were harvested at 7, 28, or 56 d following the procedure. The intimal cell layers increased substantially between 7 and 28 d following balloon dilatation with or without local drug delivery. The medial cell layers showed only a little increase. Proliferation of smooth muscle cells reached an early peak after 7 d, with a significantly higher proliferation index following local delivery. The maximum amount of macrophages in the intima and media was detected after 28 d. The lumen area decreased with time and was 0.6 +/- 0.7 mm2 in the local delivery group at 56 d compared with 0.5 +/- 0.5 mm2 in the control group. In conclusion, local delivery of Reviparin with the Dispatch catheter is safe and feasible. However, the infusion of highly concentrated low-molecular-weight heparin over a short period of time did not result in a reduction of neointima formation and restenosis following balloon dilatation in the rabbit iliac artery.

Angioplasty, Balloon, Coronary↗
PubMed1997

Angiographically undetected plaque in the left main coronary artery. Findings of intravascular ultrasound imaging.

The absence of angiographic findings despite significant coronary artery disease has been previously described. Possible explanations for the limitation of plaque detection by angiography include compensatory vessel enlargement in face of intracoronary plaque formation, the lack of reference segments in diffuse atherosclerosis as well as technical limitations. Intracoronary ultrasound (ICUS) imaging provides the possibility of direct plaque visualization. We studied angiographically normal left main coronary arteries (LMCA) in 72 patients prior to diagnostic angiography or therapeutic interventions using ICUS (30 MHz). ICUS images were continuously recorded and recalled from memory for morphometric analysis. Lumen area, plaque area and the total vessel area were determined by computer software. ICUS imaging revealed atherosclerotic plaque in 55 of the 72 patients with angiographically normal LMCA (76%). The average plaque area stenosis was 22 +/- 12% (range 3-44%). Total vessel area showed a significant direct correlation with plaque area, indicating compensation of coronary plaque formation. The average percent change in plaque area (difference between maximal and minimal plaque area within the LMCA) was 11 +/- 19%, indicating a diffuse pattern. Measurement of change in lumen area (difference between maximal and minimal lumen area within the LMCA) revealed an average value of 6 +/- 7%. Lumen area of the LMCA was 15.9 +/- 3.2 mm2 in patients with and 17.2 +/- 1.9 mm2 without atherosclerotic plaque (n.s.). Thus, the lack of angiographic changes despite advanced plaque formation in the LMCA could be explained by compensatory vessel enlargement and by diffuse distribution of plaque in the vessel; true lumen narrowings overlooked by angiography seem not to account for the failure of angiography to detect plaque.

Aged↗
PubMed1994

Regional differences in the distribution of the proteoglycans biglycan and decorin in the extracellular matrix of atherosclerotic and restenotic human coronary arteries.

Proteoglycans are important constituents of blood vessels and accumulate in various forms of vascular disease. Little is known concerning the proteoglycan composition of restenotic lesions formed after angioplasty and whether the proteoglycan composition of these lesions differs from that of primary atherosclerosis. Accordingly, we sought to characterize the distribution of two proteoglycans, biglycan and decorin, in primary atherosclerotic and restenotic lesions of human coronary arteries. Restenosis (n = 37) and primary (n = 11) lesions obtained from 48 patients by directional atherectomy of human coronary arteries were stained with antibodies against biglycan and decorin. To further characterize the extracellular matrix of restenotic tissues, we studied the co-distribution of these proteoglycans with collagen types I, III, and IV. The loose fibroproliferative tissue seen predominantly in restenosis lesions consistently stained positively for biglycan in patterns of deposition ranging from disseminated to homogeneous. The density and intensity of biglycan staining was correlated with the density of collagen type I and III fiber networks, both of which were observed to interweave among the loose fibroproliferative tissue. The compact connective tissue of primary atherosclerotic plaque was characterized by strong biglycan staining which co-localized with intense collagen type I and III staining. Only basement membrane-like structures rich in collagen type IV demonstrated negative biglycan staining. In contrast, loose fibroproliferative tissue exhibited no significant staining for decorin. Strong immunostaining for decorin, however, was found in primary atherosclerotic plaque. There are thus regional differences in the distribution of extracellular matrix proteoglycans of restenotic and primary human atherosclerotic lesions; these observations suggest that differences established for the biological roles of biglycan and decorin in other organ systems may extend as well to pathologically altered human coronary arteries.

Angioplasty, Balloon↗
PubMed1993

Arterial gene transfer using pure DNA applied directly to a hydrogel-coated angioplasty balloon.

Direct arterial gene transfer has been previously achieved using double-balloon catheters and perforated balloons, in most cases facilitated by the use of cationic liposomes or viral vectors. These gene delivery systems, however, have been compromised by issues relating to efficacy and/or safety, and furthermore require that angioplasty be performed independent of gene transfer. We investigated the possibility that arterial gene transfer might be performed during balloon angioplasty by delivery of naked genetic material from a thin coat of hydrogel polymer applied to a standard angioplasty balloon. Transfections with luciferase DNA applied to a hydrogel balloon were performed in rabbit arteries. Luciferase expression 3 days after transfection was tested in three different models: (i) an organ culture model (n = 10); (ii) surgically exposed carotid arteries (n = 14); and (iii) external iliac arteries using a percutaneous approach (n = 13). Supplementary transfections (n = 3), intended to identify the site of arterial transfection, were performed using the gene encoding for nuclear-specific beta-galactosidase (beta-gal). All rabbit arteries transfected with the luciferase gene (37/37; 100%) expressed luciferase activity. Gene expression achieved in vivo, either in the surgically exposed carotid arteries or in the external iliac arteries transfected percutaneously, was quantitatively similar to that achieved in the organ culture model. Reduction in the duration of inflation from 30 min to 1 min had no statistically significant impact on transfection efficiency. Gene expression was documented to persist up to 14 days post percutaneous transfection. Analysis of arteries transfected with nuclear-specific beta-gal showed the presence of the transgene in intimal and subintimal sites. These results demonstrate that vascular gene transfer can be performed successfully without liposomes or viral vectors using DNA applied to a standard angioplasty catheter balloon coated with hydrogel. Percutaneous transfection with a hydrogel-coated balloon permits gene transfer coincident with the angioplasty procedure itself, even with inflations as short as 1 min.

Angioplasty, Balloon↗
PubMedDate not supplied

Posttraumatic myocardial infarction with severe coronary intimal dissection documented by intravascular ultrasound.

We present a case of posttraumatic myocardial infarction after blunt chest trauma in a previously healthy man. Coronary angiography showed an eccentric occlusion in the midportion of the left anterior descending artery. Subsequent intracoronary ultrasound imaging revealed a severe intimal dissection. The outcome after intracoronary stent placement was excellent. This rare but potentially harmful complication of blunt chest trauma should be kept in mind and coronary angiography performed immediately when coronary occlusion is suspected. Intravascular ultrasound imaging is a helpful tool in the assessment of coronary artery occlusion caused by intimal dissection.

Adult↗
PubMedDate not supplied

Dislodgement of a Wiktor stent during intracoronary ultrasound examination.

We report a case of stent dislodgement complicating adjuvant intracoronary ultrasound (ICUS) imaging that required emergency coronary bypass grafting. This probably very rare complication gains importance since ICUS is increasingly used to confirm adequate stent expansion and full coverage of the lesion.

Acute Disease↗