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Robert W Thompson

Publications and source records attributed to Robert W Thompson.

At least 19 recordsLinked to original sources
PubMed2006

Molecular simulation of the adsorption of MTBE in silicalite, mordenite, and zeolite beta.

The use of methyl tertiary butyl ether (MTBE) as a gasoline additive has resulted in serious environmental problems following spills and leaks, primarily due to MTBE's high solubility in water. Remediation technologies have involved air stripping, advanced oxidation, and sorption on granular activated carbons (GAC). Hydrophobic zeolites, such as silicalite, dealuminated Y, mordenite, and beta, have been of interest in recent studies for the removal of MTBE from water. Some of these materials have shown a better performance than GAC particularly in the microg/L range. We made Monte Carlo and molecular dynamics simulations of the adsorption of pure MTBE in silicalite, mordenite, and zeolite beta with different Na+ loadings at room temperature to reveal the factors affecting the adsorption process. The results show that although the three zeolites studied here have similar pore volumes, the pore structure of zeolite beta causes a significant difference on the predicted amount of MTBE adsorbed. It was found that the position of the Na+ cations has an important effect at lower pressures. Within the range of [Na+] studied, the amount of Na+ was not found to be critical on the adsorption capacity of any of the zeolites studied, except at very low pressures in silicalite and zeolite beta.

Journal Article↗
PubMed2006

The IL-21 receptor augments Th2 effector function and alternative macrophage activation.

The IL-21 receptor (IL-21R) shows significant homology with the IL-4R, and CD4+ Th2 cells are an important source of IL-21. Here we examined whether the IL-21R regulates the development of Th2 responses in vivo. To do this, we infected IL-21R-/- mice with the Th2-inducing pathogens Schistosoma mansoni and Nippostrongylus brasiliensis and examined the influence of IL-21R deficiency on the development of Th2-dependent pathology. We showed that granulomatous inflammation and liver fibrosis were significantly reduced in S. mansoni-infected IL-21R-/- mice and in IL-21R+/+ mice treated with soluble IL-21R-Fc (sIL-21R-Fc). The impaired granulomatous response was also associated with a marked reduction in Th2 cytokine expression and function, as evidenced by the attenuated IL-4, IL-13, AMCase, Ym1, and FIZZ1 (also referred to as RELMalpha) responses in the tissues. A similarly impaired Th2 response was observed following N. brasiliensis infection. In vitro, IL-21 significantly augmented IL-4Ralpha and IL-13Ralpha1 expression in macrophages, resulting in increased FIZZ1 mRNA and arginase-1 activity following stimulation with IL-4 and IL-13. As such, these data identify the IL-21R as an important amplifier of alternative macrophage activation. Collectively, these results illustrate an essential function for the IL-21R in the development of pathogen-induced Th2 responses, which may have relevance in therapies for both inflammatory and chronic fibrotic diseases.

Animals↗
PubMed2006

Oral administration of diferuloylmethane (curcumin) suppresses proinflammatory cytokines and destructive connective tissue remodeling in experimental abdominal aortic aneurysms.

Chronic transmural inflammation and proteolytic destruction of medial elastin are key mechanisms in the development of abdominal aortic aneurysms (AAAs). Diferuloylmethane (curcumin) is a major component of the food additive tumeric, which has been shown to have anti-inflammatory properties. To determine if ingestion of curcumin influences aneurysmal degeneration, C57Bl/6 mice underwent transient elastase perfusion of the abdominal aorta to induce the development of AAAs, followed by daily oral gavage with 100 mg/kg curcumin (n = 36) or water alone (n = 31). By 14 days, mice in the control group developed a mean increase in aortic diameter of 162.8 +/- 4.6% along with a dense mononuclear inflammation and destruction of medial elastin. By comparison, the mean increase in aortic diameter in the curcumin-treated group was only 133.2 +/- 5.2% (p < 0.0001). Although aortic wall inflammation was similar between the groups, the structural integrity of medial elastin was significantly greater in curcumin-treated mice. Curcumin-treated mice also exhibited relative decreases in aortic tissue activator protein-1 and nuclear factor kappaB DNA binding activities and significantly lower aortic tissue concentrations of interleukin-1beta (IL-1beta), IL-6, monocyte chemoattractant protein-1, and matrix metalloproteinase-9 (all p < 0.05). These data demonstrate for the first time that oral administration of curcumin can suppress the development of experimental AAAs, along with structural preservation of medial elastin fibers and reduced aortic wall expression of several cytokines, chemokines, and proteinases known to mediate aneurysmal degeneration. The possibility that dietary ingestion of curcumin may have a beneficial effect in degenerative aortic aneurysms warrants further consideration.

Administration, Oral↗
PubMed2006

Localized administration of doxycycline suppresses aortic dilatation in an experimental mouse model of abdominal aortic aneurysm.

Treatment with doxycycline suppresses the development of abdominal aortic aneurysms (AAAs) in experimental animal models, but its use in humans can be accompanied by dose-related side effects. We sought to determine if localized administration of doxycycline can achieve inhibition of AAAs equivalent to that achieved by systemic treatment. C57BL/6 mice underwent transient elastase perfusion of the abdominal aorta to induce the development of AAAs. After 14 days, the mean increase in aortic diameter was reduced from 167.2+/-7.8% in untreated mice to only 129.7+/-13.8% in mice treated with 100 mg/kg/day oral doxycycline (p<0.05). Using osmotic minipumps to provide continuous periaortic infusion of doxycycline, localized infusion at rates of 0.75 to 1.0 mg/kg/day suppressed AAAs to an equivalent or even greater extent than systemic treatment [mean increase in aortic diameter 131.5+/-14.4% at 0.75 mg/kg/day, p<0.05; 103.2+/-13.5% at 1.0 mg/kg/day, p<0.01). Mean plasma doxycycline levels reached 332+/- 62 ng/mL during oral administration, but the drug was undetectable in the circulation during localized infusion. The doxycycline concentration in aortic tissue extracts was 22+/- 6 ng/mL during systemic treatment compared to only 5.6+/- 2.2 ng/mL [at 0.75 mg/kg/day] and 7.8+/- 4.0 ng/mL [at 1.0 mg/kg/day] during localized infusion (p<0.05). Localized administration of doxycycline can effectively suppress experimental AAAs with undetectable plasma drug levels, even at doses 100-fold lower than those used during oral drug administration. Localized delivery of doxycycline holds promise as a novel strategy to inhibit the progressive expansion of aortic aneurysms, perhaps as a pharmacological adjunct to endovascular (stent graft) treatment.

Administration, Oral↗
PubMed2006

A single nucleotide polymorphism in the matrix metalloproteinase 9 gene (-8202A/G) is associated with thoracic aortic aneurysms and thoracic aortic dissection.

OBJECTIVE: Matrix metalloproteinase 9 plays an important role in the maintenance of the aortic extracellular matrix. Genetic variations that affect protease expression or activity might contribute to thoracic aortic disease. The purpose of this study was to determine whether 3 single nucleotide polymorphisms in the matrix metalloproteinase 9 gene are associated with thoracic aortic aneurysms and dissection. METHODS: Genomic DNA was isolated from blood or aortic tissue from 28 patients with degenerative thoracic aortic aneurysms, 60 patients with thoracic aortic dissection, and 111 control patients. The frequency distributions of 3 matrix metalloproteinase 9 single nucleotide polymorphisms (-8202A/G, IVS4+3G/T, and 2003A/G [Q668R]) were determined by using genotyping accomplished with a real-time detection system. Associations between polymorphisms and disease were estimated with odds ratios and their 95% confidence intervals. RESULTS: The frequency of the -8202G allele was significantly higher in patients with thoracic aortic aneurysms and aortic dissection (0.52 and 0.56, respectively) than in control subjects (0.36, P < .001). Patients with thoracic aortic aneurysms or dissection were nearly 5 times more likely than control subjects to have the G allele (adjusted odds ratio, 4.87; 95% confidence interval, 2.04-11.64). There were no significant associations between the IVS4+3G/T or 2003A/G polymorphisms and thoracic aortic disease. CONCLUSIONS: The matrix metalloproteinase 9 -8202A/G polymorphism is associated with thoracic aortic aneurysms and dissection. Further studies are warranted to elucidate the functional role of the -8202A/G variant in matrix metalloproteinase 9 expression.

Adolescent↗
PubMed2006

Temporal changes in mouse aortic wall gene expression during the development of elastase-induced abdominal aortic aneurysms.

OBJECTIVE: To characterize temporal changes in mouse aortic wall gene expression associated with the development of experimental abdominal aortic aneurysms. METHODS: C57BL/6 mice underwent transient perfusion of the abdominal aorta with either elastase (n = 61) or heat-inactivated elastase as a control (n = 68). Triplicate samples of radiolabeled aortic wall complementary DNA were prepared at intervals of 0, 3, 7, 10, and 14 days, followed by hybridization to nylon microarrays (1181 genes). Autoradiographic intensity data were normalized by conversion to z scores, and differences in gene expression were defined by two-tailed z tests at a significance threshold of P < .01. RESULTS: Elastase perfusion caused a progressive increase in aortic diameter up to 14 days accompanied by transmural inflammation and destructive remodeling of the elastic media. No aneurysms occurred in the control group. Compared with healthy aorta, 336 genes exhibited significant alterations during at least 1 interval after elastase perfusion (135 at more than 1 interval and 14 at all intervals), with pronounced increases for interleukin 6, cyclin E2, interleukin 1beta, osteopontin, CD14/lipopolysaccharide receptor, P-selectin glycoprotein ligand 1, and gelatinase B/matrix metalloproteinase 9 (all >20-fold on day 3). Sixty-two genes exhibited synchronous alterations in the elastase and control groups, thus suggesting a nonspecific response. By direct comparisons between the elastase and control groups, there were 384 genes with significant differences in expression for at least 1 interval after aortic perfusion, including 234 with differential upregulation (eg, p44MAPK/ERK1, osteopontin, heat shock protein 84, hypoxia-inducible factor 1alpha, apolipoprotein E, monocyte chemotactic protein 3, MIG (monokine induced by gamma interferon), and interleukin 2 receptor gamma) and 163 with differential downregulation (eg, prothrombin, granzyme B, ataxia telangiectasia mutated, and interleukin-converting enzyme). CONCLUSIONS: Development of elastase-induced abdominal aortic aneurysms in mice is accompanied by altered aortic wall expression of genes associated with acute and chronic inflammation, matrix degradation, and vascular tissue remodeling. Knowledge of these alterations will facilitate further studies on the functional molecular mechanisms that underlie aneurysmal degeneration.

Animals↗
PubMed2006

Interleukin-5 (IL-5) augments the progression of liver fibrosis by regulating IL-13 activity.

Eosinophils are frequently found in increased numbers in a variety of chronic fibrotic diseases; however, their role in the development of hepatic fibrosis has not been dissected in vivo. Here, we used interleukin-5 (IL-5) knockout (KO) mice to determine whether eosinophils contribute to the progressive liver fibrosis that develops in response to chronic Schistosoma mansoni infection. Although infection intensities were similar in C57BL/6 and IL-5 KO mice, the average size of granulomas was significantly smaller in both acutely and chronically infected IL-5 KO mice. Their granulomas were also completely devoid of eosinophils. In addition, the knockout mice displayed over a 40% reduction in hepatic fibrosis by week 16 postinfection. The reduced fibrosis was associated with increased production of the antifibrotic cytokine gamma interferon. Moreover, although IL-13 production did not decrease consistently in the absence of IL-5, IL-13-triggered responses were substantially reduced in the granulomatous tissues. This was confirmed by analyzing the expression of several genes associated with alternative macrophage activation, including arginase 1, Fizz-1, and YM-1. Importantly, all of these IL-13-regulated genes have been linked with the mechanisms of wound healing and fibrosis. In addition to IL-5 polarizing the antigen-specific CD4+ Th2 cell response, we found that granuloma eosinophils were themselves a significant source of IL-13. Thus, by producing profibrotic mediators and polarizing the Th2 response, these findings illustrate both direct and indirect roles for eosinophils and IL-5 in the pathogenesis of schistosomiasis-induced liver fibrosis. Thus, inhibiting the activity of IL-5 or eosinophils may prove effective for a variety of chronic fibrotic diseases.

Animals↗
PubMed2006

Paragraph text reading using a pixelized prosthetic vision simulator: parameter dependence and task learning in free-viewing conditions.

PURPOSE: To investigate the feasibility of adequate reading by recipients of future prosthetic visual implants through simulation in sighted observers. METHODS: Four normally sighted subjects used a video headset to view short-story segments at a sixth grade reading level, presented in 6- to 11-word paragraphs through a pixelizing grid defined by five parameters (dot size, grid size, dot spacing, random dropout percentage, and gray-scale resolution). Grid parameters were varied individually, and four character sizes and two contrast levels were used. RESULTS: Reading speeds of 30 to 60 words per minute without errors were recorded for some parameter combinations. In general, reading accuracy and speed were influenced by all parameters. Reading accuracy exceeded 90% if the following conditions were met: At least 3 dots/charwidth were presented, and dropout did not exceed 50%. Reading speed deteriorated below 20 words per minute if accuracy fell below 90% and at low contrast if the grid spanned less than two characters. CONCLUSIONS: It is uncertain whether and to what extent retinal reorganization may limit the perception of multiple phosphenes by blind prosthesis recipients. If distinct phosphenes can be perceived, these results suggest that a 3 x 3-mm2 prosthesis with 16 x 16 electrodes should allow paragraph reading. The effects of stabilizing the dot grid on the retina must be investigated further.

Adult↗
PubMed2006

Pharmacological targets in the treatment of abdominal aortic aneurysms.

The natural history of an abdominal aortic aneurysm (AAA) is of progressive aortic wall degeneration occurring over the course of many years, ultimately, culminating in loss of structural integrity and fatal aortic rupture. Although surgical exclusion of an aneurysm can effectively prevent aortic rupture in large aneurysms, small aneurysms are generally completely asymptomatic and are very unlikely to rupture. Further, AAA can be easily diagnosed with noninvasive testing; thus, small aneurysms present an excellent opportunity for disease-modifying pharmacological intervention. Research over the past two decades has defined many of the mechanisms which result in aortic matrix degeneration in both human tissue and particularly within animal models. This has resulted in the identification of several potential targets for pharmacological intervention. Drugs directed at inhibition of the inflammatory process and matrix degrading enzymes have been successful in multiple animal models, and early evidence now suggests that disease modification with some of these agents may be successful in slowing AAA growth in humans as well. The future of AAA therapy, however, may belong to agents which can induce aneurysm regression and to delivery methods which specifically target affected arterial tissue.

Anti-Inflammatory Agents↗
PubMed2005

Analysis of binary adsorption of polar and nonpolar molecules in narrow slit-pores by mean-field perturbation theory.

In the present research study, we present the development of a model for predicting the adsorption of binary mixtures of nonpolar molecules, as well as polar molecules, based on density functional theory with mean-field approximation in narrow slit-pores. The first system under consideration is comprised of a binary mixture of nonpolar molecules, modeled by considering intermolecular dispersion forces, whereas the second system comprised of a binary mixture of polar molecules is modeled by considering orientation averaged electrostatic interactions, namely dipole-dipole and dipole-induced dipole interactions as well as dispersion interactions. An explicit equation for the Helmholtz free energy of the pore phase binary fluid mixture is derived. The proposed model is used to simulate the selective sorption of ethane from an ethane-methane mixture and water from a methanol-water mixture in the slit-pore. The simulated results are interpreted by studying the relative contributions of fluid-wall and fluid-fluid interactions. Finally, simulation results obtained are compared with the results of existing models and molecular simulations in the literature.

Journal Article↗
PubMed2005

Rapid synthesis of MFI zeolite nanocrystals.

A rapid synthesis procedure for nonagglomerated silicalite nanocrystals has been developed. This was achieved by concentrating the precursor sol before 10-12 h of aging at 80 degrees C, followed by hydrothermal synthesis at 175 degrees C for 90 min. The high silica concentration in the concentrated sol accelerated the aggregation of primary units that were present early in the system. Thus, little silica nutrients were left for growth when the secondary particles were converted to zeolite during hydrothermal reaction. As a result, fully dispersible nanocrystals were obtained within a day instead of weeks as reported previously. The aggregation of primary units during the 80 degrees C aging process as well as the conversion of these aggregates into zeolite has been followed by DLS, XRD, and FTIR. In light of the new results, the nucleation and growth mechanisms of MFI zeolite that have been under debate in the literature were reexamined.

Crystallization↗
PubMed2005

Neutrophil depletion inhibits experimental abdominal aortic aneurysm formation.

BACKGROUND: Neutrophils may be an important source of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two matrix-degrading enzymes thought to be critical in the formation of an abdominal aortic aneurysm (AAA). The purpose of this investigation was to test the hypothesis that neutrophil depletion would limit experimental AAA formation by altering one or both of these enzymes. METHODS AND RESULTS: Control, rabbit serum-treated (RS; n=27) or anti-neutrophil-antibody-treated (anti-PMN; n=25) C57BL/6 mice underwent aortic elastase perfusion to induce experimental aneurysms. Anti-PMN-treated mice became neutropenic (mean, 349 cells/microL), experiencing an 84% decrease in the circulating absolute neutrophil count (P<0.001) before elastase perfusion. Fourteen days after elastase perfusion, control mice exhibited a mean aortic diameter (AD) increase of 104+/-14% (P<0.0001), and 67% developed AAAs, whereas anti-PMN-treated mice exhibited a mean AD increase of 42+/-33%, with 8% developing AAAs. The control group also had increased tissue neutrophils (20.3 versus 8.6 cells per 5 high-powered fields [HPFs]; P=0.02) and macrophages (6.1 versus 2.1 cells per 5 HPFs, P=0.005) as compared with anti-PMN-treated mice. There were no differences in monocyte chemotactic protein-1 or macrophage inflammatory protein-1alpha chemokine levels between groups by enzyme-linked immunosorbent assay. Neutrophil collagenase (MMP-8) expression was detected only in the 14-day control mice, with increased MMP-8 protein levels by Western blotting (P=0.017), and MMP-8-positive neutrophils were seen almost exclusively in this group. Conversely, there were no statistical differences in MMP-2 or MMP-9 mRNA expression, protein levels, enzyme activity, or immunostaining patterns between groups. When C57BL/6 wild-type (n=15) and MMP-8-deficient mice (n=17) were subjected to elastase perfusion, however, ADs at 14 days were no different in size (134+/-7.9% versus 154+/-9.9%; P=0.603), which suggests that MMP-8 serves only as a marker for the presence of neutrophils and is not critical for AAA formation. CONCLUSIONS: Circulating neutrophils are an important initial component of experimental AAA formation. Neutrophil depletion inhibits AAA development through a non-MMP-2/9-mediated mechanism associated with attenuated inflammatory cell recruitment.

Animals↗
PubMed2005

Observations on clear solution silicalite-1 growth by nanoslabs.

Several research groups have reported the presence of nanometer-sized particles (nanoslabs) in clear solutions, which precipitate the crystalline MFI (ZSM-5) structure. Debate about the growth mechanism for Al-free ZSM-5 (silicalite-1) has revolved around growth by small silicate units (monomers, dimers, etc.) from solution vs growth by nanoslab addition. A model developed for precipitation of uniform sized colloids by addition of sub-colloidal precursor units has been adapted for this zeolite synthesis system. Parameter values were adjusted for the simulation results to match experimental observations from work reported previously, at least to the extent possible. The model involved the simultaneous solution of up to 6000 ordinary differential equations, and required computation times of up to 24 h. The results shed light on the crystal growth mechanism, but pose questions for further investigations of the nucleation mechanism.

Journal Article↗
PubMed2005

Matrix metalloproteinases in ascending aortic aneurysms: bicuspid versus trileaflet aortic valves.

BACKGROUND: Abnormal matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) expression contributes to the development of abdominal aortic aneurysms. Recent data suggest that MMP-2 and MMP-9 may also play a role in thoracic aortic disease. We sought to determine (1) whether ascending aortic aneurysms are associated with increased MMP expression and (2) whether aortic inflammation and MMP expression differ between patients with congenital bicuspid aortic valves (BAVs) and those with trileaflet aortic valves (TAVs). MATERIALS AND METHODS: Samples of ascending aortic aneurysms were obtained from 29 patients; 14 patients had BAVs and 15 had TAVs. Control ascending aorta was obtained from 14 organ donors or heart transplant recipients. Aortic histology and immunohistochemistry were performed to evaluate elastin degradation, inflammatory changes, and MMP-2 and MMP-9 expression. Aortic levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured using ELISA. RESULTS: Aneurysms in the TAV patients exhibited marked inflammation, high CD68 expression, diminished elastin content, increased MMP-9 expression, and normal MMP-2 levels. In contrast, BAV aneurysms were characterized by a relative lack of inflammation, preservation of elastin content, normal MMP-9 levels, and elevated MMP-2 expression. TIMP-1 and TIMP-2 levels were not significantly different among the three groups. CONCLUSIONS: Ascending aortic aneurysms exhibited increased MMP expression. The pattern of MMP expression and the degree of inflammation, however, differed between aneurysms associated with BAVs and those with TAVs. Variations in the molecular mechanisms underlying different types of thoracic aortic aneurysms warrant further investigation.

Adult↗
PubMed2005

Suppression of experimental abdominal aortic aneurysms in mice by treatment with pyrrolidine dithiocarbamate, an antioxidant inhibitor of nuclear factor-kappaB.

OBJECTIVE: Proinflammatory cytokines and matrix metalloproteinases (MMPs) are prominent mediators of the connective tissue destruction that characterizes abdominal aortic aneurysms (AAAs), and nuclear factor (NF)-kappaB is a cytokine-responsive transcription factor that promotes macrophage MMP expression. The purpose of this study was to determine whether aneurysmal degeneration is influenced by pyrrolidine dithiocarbamate (PDTC), a pharmacologic inhibitor of NF-kappaB. METHODS: Adult male C57BL/6 mice underwent transient elastase perfusion of the abdominal aorta to induce the development of AAAs. Animals were treated every 48 hours by intraperitoneal injection with either saline (n = 34) or PDTC 20 mg/kg (n = 49). Aortic diameter (AD) measurements were used to determine the extent of aortic dilatation before and immediately after elastase perfusion and again at day 14. RESULTS: All saline-treated mice developed AAAs associated with mononuclear inflammation and destruction of medial elastin (overall increase in AD, mean +/- SEM, 169.1% +/- 7.5%). In contrast, the incidence of AAAs was only 63% in PDTC-treated mice, with a reduction in the overall increase in AD to 109.8% +/- 4.2% ( P < .0001 vs saline), decreased inflammation, and structural preservation of aortic wall connective tissue. Although aneurysm development in saline-treated mice was associated with a marked increase in aortic tissue NF-kappaB and activator protein 1 DNA-binding activities, both activities were substantially reduced in PDTC-treated animals. PDTC-treated mice also exhibited significantly lower serum and aortic wall concentrations of interleukin 1beta and interleukin 6, as well as lower amounts of aortic wall MMP-9, as compared with saline-treated controls. CONCLUSIONS: Treatment with PDTC inhibits elastase-induced experimental AAAs in the mouse, along with suppression of aortic wall NF-kappaB and activator protein 1 transcription factor activities, reduced expression of proinflammatory cytokines, and suppression of MMP-9. NF-kappaB is therefore a potentially important therapeutic target for the suppression of aneurysmal degeneration. CLINICAL RELEVANCE: Development and progression of human AAAs is associated with inflammation and enzymatic degradation of connective tissue proteins. MMP-9 is one of the enzymes involved in aneurysm disease, and its production may be induced in part by activation of the transcription factor NF-kappaB. In this mouse model, treatment with pyrrolidine dithiocarbamate (a pharmacologic inhibitor of NF-kappaB) acted to suppress MMP-9 and aneurysm development. It is hoped that treatment strategies that target NF-kappaB may eventually be shown to suppress the growth of small aortic aneurysms in patients.

Animals↗
PubMed2005

Decreased expression of fibulin-5 correlates with reduced elastin in thoracic aortic dissection.

BACKGROUND: Thoracic aortic aneurysmal diseases are characterized by degeneration of elastin within the aortic wall. Although proteinases, such as matrix metalloproteinase, appear to contribute to elastin degradation, little is known about the role of elastic fiber assembly in such diseases. Fibulin-5 is an extracellular protein that is expressed in the vascular basement membrane and regulates elastic fiber assembly by microfibril machinery. In this study, we examined whether thoracic aortic dissection (TAD) is associated with abnormal fibulin-5 expression. METHODS: Intraoperative aortic samples were obtained from 21 patients with proximal aortic dissection. Control aortic tissue was obtained from 11 organ donors, heart transplant recipients, and patients undergoing coronary artery bypass. An in vitro culture of vascular smooth muscle cells was obtained from 2 TAD patients and 1 control subject. To evaluate elastin expression, we stained tissue sections with Verhoeff-Van Gieson stain. Fibulin-5 messenger RNA (mRNA) expression was determined by quantitative real-time reverse-transcriptase-polymerase chain reaction. RESULTS: Aortic fibulin-5 mRNA and elastin content were decreased in TAD patients, compared with controls (P=.001 and P=.02, respectively). Decreased fibulin-5 expression strongly correlated with decreased amounts and fragmentation of elastin in aortic samples from patients with TAD (r=0.83, P < .0001 and F=20.7, P < .0001 respectively). The fibulin-5 mRNA in aortic vascular smooth muscle cells collected from TAD demonstrated a 38% decrease in expression, compared with the control. CONCLUSIONS: Patients with proximal aortic dissection exhibited significantly decreased expression of aortic fibulin-5. Decreased fibulin-5 may contribute to the pathogenesis of aortic dissection by impairing elastic fiber assembly.

Aged↗
PubMed2005

Treatment with simvastatin suppresses the development of experimental abdominal aortic aneurysms in normal and hypercholesterolemic mice.

OBJECTIVE: To determine if treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) can influence the development of experimental abdominal aortic aneurysms (AAAs). SUMMARY BACKGROUND DATA: AAAs are associated with atherosclerosis, chronic inflammation, and matrix metalloproteinase (MMP)-mediated connective tissue destruction. Because statins exert antiinflammatory activities independent of their lipid-lowering effects, these agents may help suppress aneurysmal degeneration. METHODS: C57Bl/6 wild-type and hypercholesterolemic apoE-deficient mice underwent transient perfusion of the aorta with elastase followed by subcutaneous treatment with either 2 mg/kg simvastatin per day or vehicle. Aortic diameter (AD) was measured before and 14 days after elastase perfusion. The extent of aortic dilatation (DeltaAD) was determined with AAAs defined as DeltaAD >100%. RESULTS: Wild-type mice treated with simvastatin exhibited a 21% reduction in DeltaAD and a 33% reduction in AAAs compared with vehicle-treated controls. Suppression of AAAs in simvastatin-treated mice was associated with preservation of medial elastin and vascular smooth muscle cells, as well as a relative reduction in aortic wall expression of MMP-9 and a relative increase in expression of TIMP-1. In hypercholesterolemic apoE-deficient mice, treatment with simvastatin was associated with a 26% reduction in DeltaAD and a 30% reduction in AAAs. Treatment with simvastatin had no effect on serum cholesterol levels in either normal or hypercholesterolemic mice. CONCLUSIONS: Treatment with simvastatin suppresses the development of experimental AAAs in both normal and hypercholesterolemic mice. The mechanisms of this effect are independent of lipid-lowering and include preservation of medial elastin and smooth muscle cells, as well as altered aortic wall expression of MMPs and their inhibitors.

Animals↗