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Results for “Remodeling”

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PubMed1990

An approach for time-dependent bone modeling and remodeling-application: a preliminary remodeling simulation.

In a companion paper, we presented a time-dependent theory for bone modeling and remodeling in response to a daily loading history. This paper represents a preliminary attempt to use the theory to determine the distribution of bone density within the adult proximal femur under an assumed normal loading history. Subsequent functional adaptation of the internal structure due to changes in the loading history are then determined. Throughout this preliminary study, the external geometry of the proximal femur is considered to be fixed, i.e., changes in the external shape are neither stimulated nor allowed. Linear and trilinear (dead-zone nonlinearity) rate remodeling laws were compared. Computer emulations using two-dimensional finite element models were successful in creating a normal-appearing distribution of bone tissue when remodeling was initiated from a solid structure of homogeneous bone density. Subsequent reduction in the loading history caused regional bone atrophy. Reinstatement of the normal loading history caused a generalized increase in bone mass but resulted in a slightly different bone distribution than was calculated for a constant loading history. These results demonstrate the utility of the remodeling theory and are consistent with the hypothesis that similar stress-related phenomena are responsible for both normal morphogenesis and functional adaptation in response to changes in the bone loading.

Animals↗

PubMed2006

Could activated tissue remodeling be considered as early marker for progressive valve degeneration? Comparative analysis of checkpoint and ECM remodeling gene expression in native degenerating aortic valves and after bioprosthetic replacement.

OBJECTIVES: Aortic stenosis is the leading cause of heart valve disease in elderly. Little is known about molecular mechanisms leading to altered left ventricular geometry generally and, particularly, to remodeling of degenerating aortic valve. Alterations in native degenerating aortic valves and valvular tissue after replacement might result from a stage specific tissue remodeling protein core induced by stress responsible factors. Here we were looking for a possible stage specificity of tissue remodeling and stress responsive checkpoint gene activation in native degenerating human aortic valves and bioprosthetic valvular tissue after replacement. MATERIALS AND METHODS: Specimens of native degenerating aortic valves as well as bioprosthetic valves after replacement were tested for their morphological properties. Native degenerating valves were selected for two groups: non-calcified (7 samples) and calcified (5 samples) one; the third group (5 samples) was consisting of bioprosthetic valve samples after replacement. Individual mRNA-pools were isolated from each tissue sample, and semi-quantitative RT-PCR was performed. Target transcripts of p21(waf1/cip1), MT1-MMP, MMP-2, MMP-9 and TIMP-1 were measured. The specificity was controlled by restriction analysis of PCR products. RESULTS AND CONCLUSIONS: According to the abundant expression of p21(waf1/cip1), a highly activated stress response was found in non-calcified native degenerating aortic valves, whereas no stress response was monitored in valvular tissue after replacement. Whereas MT1-MMP expression was almost equally induced in all three groups investigated, MMP-9 was higher expressed in non-calcified versus calcified native valves, and was not expressed after replacement. An induced expression of MMP-2 was detected in non-calcified native degenerating aortic valves only. An abundant expression of tissue inhibitor of metalloproteinases TIMP-1 was observed in all three groups tested. Apparently, the ECM degradation potential is specifically enhanced in non-calcified native degenerating aortic valves e.g. at the early degeneration stages. In contrast, the replaced valves were found to be actively resorbing tissue with no detectable stress response, where both MT1-MMP and TIMP-1 might play the key role in geometry remodeling.

Aged↗

PubMed1987

Quantitation of maxillary remodeling. 2. Masking of remodeling effects when an "anatomical" method of superimposition is used in the absence of metallic implants.

We report the results of a study aimed at quantifying the differences in the perceived pattern of maxillary remodeling that are observed when different methods are used to superimpose maxillary images in roentgenographic cephalometrics. In a previous article, we reported cumulative changes in the positions of anterior nasal spine (ANS), posterior nasal spine (PNS), and Point A for a sample of 31 subjects with maxillary metallic implants. Measurements had been made on lateral cephalograms taken at annual intervals relative to superimposition on the implants. In the present article, we quantify the differences in the perceived displacement of the same landmarks in the same sample when a standard "anatomical best bit" rule was used in lieu of superimposition on the implants. The anatomical best fit superimposition as herein defined was found in this sample to lose important information on the downward remodeling of the superior surface of the maxilla that had been detected when the implant superimposition was used. In fact, we observed a small artifactual upward displacement of the ANS-PNS line. In the anteroposterior direction, the tendency toward backward displacement of skeletal landmarks through time that had been detected with the implant superimposition was replaced by a small forward displacement of ANS and Point A together with reduced backward displacement of PNS. To the extent that the implant superimposition is to be considered the true and correct one, the anatomical best fit superimposition appears to understate the true downward remodeling of the palate by an average of about 0.3 and 0.4 mm per year, although this value differs at different ages and timepoints. The anatomical best fit superimposition also misses entirely the small mean tendency toward backward remodeling that was observed when the implant superimposition was used. In situations in which there are no implants, clinicians and research workers must necessarily continue to use anatomically based superimpositions with definitions more or less similar to that of the anatomical best fit superimposition used here. When they do so, some systematic errors will be incurred. For grouped data, we believe that the best currently available estimates of the mean errors involved in using the anatomical best fit superimposition to approximate an implant superimposition are the "bias" values included in Table IIC. The secondary implications of these differences to the perceived displacements of the maxillary teeth will be considered in our next article.

Adolescent↗

PubMed2006

Acute myocardial infarction: clinical characteristics and plaque morphology between expansive remodeling and constrictive remodeling by intravascular ultrasound.

BACKGROUND: According to recent intravascular ultrasound (IVUS) studies, expansive remodeling (ER) at the culprit lesion has been observed in almost 50% of patients with acute coronary syndrome and constrictive remodeling (CR) in 30%. The purpose of this study is to investigate the difference between ER and CR at the culprit lesion in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Preinterventional IVUS images of 73 patients with AMI were identified. The remodeling index (RI) was defined as the ratio of the external elastic membrane (EEM) areas at the culprit lesion to the EEM areas at the proximal reference site. Expansive remodeling was defined as an RI > 1.05; CR, as an RI < 0.95. In patients with AMI, 40 patients (55%) showed ER on IVUS, whereas CR was observed in 18 patients (25%). Patients with ER were significantly older than those with CR (P < .005). The frequency of the presence of calcifications was higher in patients with ER than in those with CR (P < .0005). In patients with AMI with ER, soft plaque with small calcium was the most frequent (58%). Multivariate analysis revealed that age and the presence of calcifications remained as independent predictors of ER. CONCLUSIONS: These findings suggest that ER relates to old age and calcification, and CR may contribute to early plaque progression than ER in patients with AMI.

Age Factors↗

PubMed2006

Remodeling index compared to actual vascular remodeling in atherosclerotic left main coronary arteries as assessed with long-term (> or =12 months) serial intravascular ultrasound.

OBJECTIVES: We present the remodeling index (RI) versus serial intravascular ultrasound (IVUS) data. BACKGROUND: The RI, derived by comparing lesion external elastic membrane (EEM) cross-sectional area versus the reference at one time point, is used in various IVUS studies as a substitute of true remodeling (change in EEM over time), assuming that it represents true remodeling. METHODS: We studied 46 non-stenotic left main arteries using serial IVUS (follow-up 18 +/- 8 months). Plaques were divided into subgroups according to the follow-up RI: follow-up RI >1 (n = 27) versus follow-up RI < or =1 (n = 19). RESULTS: Lesions with a follow-up RI >1 had an increase in lumen despite an increase in plaque because of an increase in EEM. Conversely, lesions with a follow-up RI < or =1 had a reduction in lumen as a result of both a plaque increase and EEM decrease. Overall, the follow-up RI correlated directly with changes in lesion site EEM (baseline-to-follow-up). Although there was no correlation between the follow-up RI and changes in reference EEM area, changes in reference EEM area did correlate directly with changes in lesion EEM area. In nearly 90% of lesions with a follow-up RI >1, there was a previously documented increase in EEM area. Using multivariate linear regression analysis, the follow-up RI was dependent on the baseline RI, the increase in lesion EEM area, and the decrease in reference EEM area. The follow-up RI was not dependent on changes in lesion plaque area. CONCLUSIONS: The vast majority of left main lesions with a remodeling index >1 had evidence of a previous increase in lesion-site EEM area.

Aged↗

PubMed2006

Chromatin remodelling in mammalian differentiation: lessons from ATP-dependent remodellers.

The initiation of cellular differentiation involves alterations in gene expression that depend on chromatin changes, at the level of both higher-order structures and individual genes. Consistent with this, chromatin-remodelling enzymes have key roles in differentiation and development. The functions of ATP-dependent chromatin-remodelling enzymes have been studied in several mammalian differentiation pathways, revealing cell-type-specific and gene-specific roles for these proteins that add another layer of precision to the regulation of differentiation. Recent studies have also revealed a role for ATP-dependent remodelling in regulating the balance between proliferation and differentiation, and have uncovered intriguing links between chromatin remodelling and other cellular processes during differentiation, including recombination, genome organization and the cell cycle.

Adenosine Triphosphatases↗

PubMed2001

Anti-remodelling drugs for the treatment of asthma: requirement for animal models of airway wall remodelling.

1. Airway wall remodelling (AWR), the structural change induced by acute and chronic inflammation in the airways, may be one of the most significant and difficult to reverse components of progressive asthma. 2. The mechanisms underlying the development of AWR are not known. Studies of only the most superficial wall structures of large airways can be conducted in living humans because of the degree of invasiveness required to measure airway structural changes. These studies reveal that currently available agents do not fully prevent or reverse AWR. Thus, animal models of asthma pathology may be used to assess the contribution of particular mediators and cells to the development of remodelling and may also prove to be useful in the initial screening of potential anti-remodelling agents. 3. Airway hyperresponsiveness and AWR stimulated by chronic antigen challenge in previously disease-free animals is the most popular of the currently used models of remodelling. Other animal models include the use of specially bred strains with intrinsic airway hyperresponsiveness or animals that have a naturally occurring asthma-like disease, such as cats with feline asthma or horses with heaves. The further development of animal models of AWR will facilitate the development of novel anti-asthma therapies.

Airway Obstruction↗

PubMed2000

Artificially recruited TATA-binding protein fails to remodel chromatin and does not activate three promoters that require chromatin remodeling.

Transcriptional activators are believed to work in part by recruiting general transcription factors, such as TATA-binding protein (TBP) and the RNA polymerase II holoenzyme. Activation domains also contribute to remodeling of chromatin in vivo. To determine whether these two activities represent distinct functions of activation domains, we have examined transcriptional activation and chromatin remodeling accompanying artificial recruitment of TBP in yeast (Saccharomyces cerevisiae). We measured transcription of reporter genes with defined chromatin structure by artificial recruitment of TBP and found that a reporter gene whose TATA element was relatively accessible could be activated by artificially recruited TBP, whereas two promoters, GAL10 and CHA1, that have accessible activator binding sites, but nucleosomal TATA elements, could not. A third reporter gene containing the HIS4 promoter could be activated by GAL4-TBP only when a RAP1 binding site was present, although RAP1 alone could not activate the reporter, suggesting that RAP1 was needed to open the chromatin structure to allow activation. Consistent with this interpretation, artificially recruited TBP was unable to perturb nucleosome positioning via a nucleosomal binding site, in contrast to a true activator such as GAL4, or to perturb the TATA-containing nucleosome at the CHA1 promoter. Finally, we show that activation of the GAL10 promoter by GAL4, which requires chromatin remodeling, can occur even in swi gcn5 yeast, implying that remodeling pathways independent of GCN5, the SWI-SNF complex, and TFIID can operate during transcriptional activation in vivo.

Chromatin↗

PubMed2006

Structural atrial remodeling alters the substrate and spatiotemporal organization of atrial fibrillation: a comparison in canine models of structural and electrical atrial remodeling.

Several animal models of atrial fibrillation (AF) have been developed that demonstrate either atrial structural remodeling or atrial electrical remodeling, but the characteristics and spatiotemporal organization of the AF between the models have not been compared. Thirty-nine dogs were divided into five groups: rapid atrial pacing (RAP), chronic mitral regurgitation (MR), congestive heart failure (CHF), methylcholine (Meth), and control. Right and left atria (RA and LA, respectively) were simultaneously mapped during episodes of AF in each animal using high-density (240 electrodes) epicardial arrays. Multiple 30-s AF epochs were recorded in each dog. Fast Fourier transform was calculated every 1 s over a sliding 2-s window, and dominant frequency (DF) was determined. Stable, discrete, high-frequency areas were seen in none of the RAP or control dogs, four of nine MR dogs, four of six CHF dogs, and seven of nine Meth dogs in either the RA or LA or both. Average DFs in the Meth model were significantly greater than in all other models in both LA and RA except LA DFs in the RAP model. The RAP model was the only one with a consistent LA-to-RA DF gradient (9.5 +/- 0.2 vs. 8.3 +/- 0.3 Hz, P < 0.00005). The Meth model had a higher spatial and temporal variance of DFs and lower measured organization levels compared with the other AF models, and it was the only model to show a linear relationship between the highest DF and dispersion (R(2) = 0.86). These data indicate that structural remodeling of atria (models known to have predominantly altered conduction) leads to an AF characterized by a stable high-frequency area, whereas electrical remodeling of atria (models known to have predominantly shortened refractoriness without significant conduction abnormalities) leads to an AF characterized by multiple high-frequency areas and multiple wavelets.

Animals↗

PubMed2003

Sensitivity and specificity of QCA in detecting coronary arterial remodeling after intracoronary brachytherapy: a comparison to serial volumetric three-dimensional intravascular ultrasound analysis. Can we detect positive remodeling by luminography?

BACKGROUND: After treatment with intracoronary brachytherapy, enlargement of lumen (negative late loss) at follow-up has been demonstrated. The aim of the study is to analyze the sensitivity and specificity of quantitative coronary angiography (QCA) parameters to detect a positive vessel remodeling after intracoronary -radiation as compared to intravascular ultrasound (IVUS). METHODS: Twenty-seven patients (27 vessels) treated with balloon angioplasty followed by catheter-based intracoronary -radiation with a (90)Strontium/(90)Yttrium source were assessed by both QCA and three-dimensional IVUS with electrocardiogram-gated pullback. Irradiated segments were analyzed over the total treatment length and in subsegment lengths of 5 mm. RESULTS: Change in minimum luminal diameter (MLD) was not a predictor for the positive remodeling in either total irradiated segments or 5 mm subsegments, with a 54.3% ROC curve area [95% confidence interval (CI), 30-79%], sensitivity of 39% and specificity of 44% (p = not significant) in the total irradiated segments and a 55.9% ROC curve area (95% CI, 46-66%), sensitivity of 55% and specificity of 54% (p = not significant) in the 5 mm subsegments. Changes in mean and maximal lumen diameter were not significant parameters to detect positive vessel remodeling. When only central subsegments were analyzed, change in MLD was a significant predictor, with a 63.3% ROC curve area (95% CI, 52-75%), sensitivity of 55% and specificity of 64% (p = 0.029). CONCLUSION: Lumen enlargement detected by QCA does not reliably indicate a positive vessel remodeling after intracoronary radiation. IVUS analysis may be necessary to investigate the mechanism of restenosis after balloon angioplasty followed by catheter-based radiation.

Angioplasty, Balloon, Coronary↗

PubMed2001

Endothelin-1 promotes vascular structural remodeling during the progression of heart failure prevention of vascular remodeling using a specific endothelin-converting enzyme inhibitor.

To evaluate the effects of endothelin (ET)-converting enzyme (ECE) inhibitor on vascular remodeling in dogs with congestive heart failure (CHF), we chronically administered an ECE inhibitor, FR901533 (FR, iv. 0.3mg/kg/hr, n=6), to dogs with CHF induced by rapid ventricular pacing. Vehicle CHF dogs were given saline (n=7). In the vehicle CHF group after 3 weeks of pacing, the ET system was activated in the plasma and vasculature (3 and 5 times higher than normal, respectively). Inward remodeling occurred in the femoral artery; medial thickness (MT, 225+/-5 vs 193+/-4 microm, P<0.05) and deposition of collagen (DC, 22+/-2 vs 17+/-1%, P<0.01) significantly increased, while lumen diameter (LD, 1173+/-39 vs 1481+/-44 microm, P<0.05) decreased in the femoral artery with CHF compared with the normal femoral artery. There were significant correlations between the number of ET-1 positive cells and MT, DC, LD and systemic vascular resistance. FR significantly suppressed the changes in these vascular parameters compared with the changes in the vehicle CHF group despite the lack of an effect on blood pressure, and moreover FR caused decreases in ET-1 levels in both the plasma and femoral artery (reduced to 43% and 54%, respectively, of the levels in the vehicle CHF group, P<0.05). In conclusion, ET-1 plays a critical role in the structural deterioration of the vasculature during the progression of CHF, and ECE inhibitors can prevent the development of vascular remodeling.

Animals↗

PubMed2001

Rationale and design for the SARIS trial; effect of statin on atherosclerosis and vascular remodeling assessed with intravascular sonography. Effect of Statin on Atherosclerosis and vascular Remodeling assessed with Intravascular Sonography.

PURPOSE: The SARIS study (effect of Statin on Atherosclerosis and vascular Remodeling assessed with Intravascular Sonography) is a prospective randomized multicenter trial designed to assess both morphological and functional cardiovascular effects of atorvastatin. METHODS: Participating centers will include 50 patients with normal to mildly elevated cholesterol levels eligible for balloon angioplasty and/or stent placement of the common iliac artery. Patients will be randomized to 1-year treatment with either low-dose (10 mg) or high-dose (80 mg) atorvastatin. The morphological effects of atorvastatin will be studied using intravascular ultrasound (IVUS); the effect of atorvastatin on both plaque volume and vascular remodeling seen at 1-year follow-up will be investigated. The functional cardiovascular effects of atorvastatin will be studied using dobutamine stress echocardiography (DSE); the effect of atorvastatin on myocardial coronary flow reserve at 6-months and 1-year follow-up will be investigated. The aims of the present study are noteworthy in respect that (1) IVUS is the only available technique to sensitively measure the effect of atorvastatin on both intimal hyperplasia and vascular remodeling, and (2) DSE is a non-invasive test to objectively quantify the effect of atorvastatin on the functionality of the coronary artery.

Anticholesteremic Agents↗

PubMed2005

ATP-dependent chromatin-remodeling complexes in DNA double-strand break repair: remodeling, pairing and (re)pairing.

The genomic integrity of a eukaryotic cell is challenged by over 10,000 chromosomal lesions per day. Therefore the cell has evolved efficient mechanisms to recognize, signal, and repair DNA breaks. Defects in any of these steps can lead to chromosomal aberrations and cancers. As these lesions must be repaired in the context of chromatin, both chromatin-modifying and nucleosome-remodeling enzymes have been implicated in DNA damage repair. We reported recently that the RSC and Swi/Snf ATP-dependent chromatin-remodeling complexes are involved in DSB repair specifically by homologous recombination. Here we discuss how such enzymes might be recruited to DNA breaks, why so many remodelers are recruited to sites of DSBs, and a possible functional connection between RSC's roles in sister chromatid cohesion and DSB repair.

Adenosine Triphosphatases↗

PubMed2003

Beneficial effects of angiotensin-converting enzyme inhibitor and nitrate association on left ventricular remodeling in patients with large acute myocardial infarction: the Delapril Remodeling after Acute Myocardial Infarction (DRAMI) trial.

BACKGROUND: In the large-scale trial, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-3 (GISSI-3), patients receiving the combination of lisinopril and glyceryl trinitrate benefited most from experimental therapy. Therefore, a multicenter, randomized, double-blind study, Delapril Remodeling After Acute Myocardial Infarction (DRAMI), was designed to assess (1) the possible additive beneficial effect on left ventricular remodeling of nitrates when combined with an angiotensin-converting enzyme inhibitor (ACEI), and (2) the tolerability of a new ACEI, delapril, in respect to lisinopril in patients with large myocardial infarction (MI). METHODS: A total of 177 patients were randomized to receive delapril plus isosorbide-5-mononitrate (IS5MN) placebo, delapril plus IS5MN, lisinopril plus IS5MN placebo, or lisinopril plus IS5MN starting within the first 36 hours after the onset of symptoms and continuing for 3 months. RESULTS: More than 80% of the patients showed extensive ST-segment changes and 36.7% had signs or symptoms of heart failure during the first 36 hours. Over 3 months, IS5MN reduced, by 76%, the increase in LVEDV (17.4 +/- 5.0 mL placebo vs 4.2 +/- 4.4 mL IS5MN, P =.0439), reversed the increase in LVESV (7.5 +/- 3.9 mL placebo vs -5.5 +/- 2.9 mL IS5MN, P =.0052), and increased the recovery of LVEF (1.9% +/- 1.3% placebo vs 6.7% +/- 1.2% IS5MN, P =.0119). Overall, 3-month mortality was 10.2%; the most frequent clinical events were new episodes of severe heart failure (18.1%), persistent hypotension (10.7%), and post-MI angina (18.1%), with no differences between treatment groups. CONCLUSIONS: Administration for 3 months of IS5MN combined with an ACEI, both started within 36 hours from the onset of symptoms, was safe and effective in reducing LV dilation and dysfunction after MI. The 2 ACEIs, delapril and lisinopril, appeared to be equally well tolerated.

Aged↗

PubMed2006

Effects of selective matrix metalloproteinase inhibitor (PG-116800) to prevent ventricular remodeling after myocardial infarction: results of the PREMIER (Prevention of Myocardial Infarction Early Remodeling) trial.

OBJECTIVES: We sought to determine whether matrix metalloproteinase (MMP) inhibitor, PG-116800, reduced left ventricular (LV) remodeling after myocardial infarction (MI). BACKGROUND: PG-116800 is an oral MMP inhibitor with significant antiremodeling effects in animal models of MI and ischemic heart failure. METHODS: In an international, randomized, double-blind, placebo-controlled study, 253 patients with first ST-segment elevation MI and ejection fraction between 15% and 40% were enrolled 48+/- 24 h after MI and treated with placebo or PG-116800 for 90 days. Major efficacy end points were changes in LV volumes as determined by serial echocardiography, and clinical and safety outcomes were also collected. RESULTS: In total, 203 patients (80%) completed 90 days of treatment and had evaluable baseline and 90-day echocardiograms. The proportion of patients with anterior MI (78% vs. 81%) and primary percutaneous coronary intervention (90% vs. 91%) along with baseline LV ejection fraction (35.5% vs. 36.8%) did not differ between PG-116800-treated and placebo-treated patients. There was no difference in the change in LV end-diastolic volume index from days 0 to 90 with PG-116800 versus placebo (5.09 +/- 1.45 ml/m(2) vs. 5.48 +/- 1.41 ml/m2, p = 0.42). Changes in LV diastolic volume, LV systolic volume, LV ejection fraction, sphericity index, plus rates of death or reinfarction were not significantly improved with PG-116800. PG-116800 was well tolerated; however, there was increased incidence of arthralgia and joint stiffness without significant increase in overall musculoskeletal adverse events (21% vs. 15%, p = 0.33). CONCLUSIONS: Matrix metalloproteinase inhibition with PG-116800 failed to reduce LV remodeling or improve clinical outcomes after MI.

Angioplasty, Balloon, Coronary↗

PubMed2001

Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate whether plasma aldosterone (ALD) is extracted or produced through the heart in patients with acute myocardial infarction (AMI) and to determine the relationship between transcardiac extraction of plasma ALD and left ventricular (LV) remodeling. BACKGROUND: Although we demonstrated that circulating ALD was extracted through the failing heart and that transcardiac extraction of ALD correlated with LV end-diastolic volume index (LVEDVI) in patients with congestive heart failure, the existence and increase of ALD synthase in the hearts of infarct rats were reported, suggesting cardiac production of ALD in patients with AMI. METHODS: We measured plasma ALD in the aortic root (Ao) and coronary sinus (CS) in 57 consecutive patients who received successful revascularization and enalapril, with first AMI at acute phase and after one month. We also measured plasma procollagen type III aminoterminal peptide (PIIINP) in the CS. RESULTS: Plasma ALD was significantly lower in the CS than it was in the Ao at the acute phase (84.7 +/- 6.3 pg/ml vs. 105.5 +/- 8.0 pg/ml, p < 0.0001). Significant positive correlations exist between the transcardiac gradient of ALD at the acute phase and the LVEDVI at one month. Moreover, the transcardiac gradient of plasma ALD at the acute phase has a significant correlation with plasma PIIINP, a biochemical marker of fibrosis, after one month. Stepwise multivariate analysis showed that transcardiac extraction of plasma ALD at the acute phase had an independent and significant positive relationship with a large LVEDVI after one month. CONCLUSIONS: These results indicate that plasma ALD is extracted through the heart in patients with AMI at the acute phase and that the extracted ALD plays an important role in modulating post-infarct LV remodeling.

Acute Disease↗

PubMed2001

Airway wall remodelling and hyperresponsiveness: modelling remodelling in vitro and in vivo.

Airway wall remodelling contributes to the airway hyperresponsiveness that characterizes asthma. An increase in airway smooth muscle (ASM) volume is quantitatively important in the overall remodelling response and may be considered as a target for new therapeutic approaches to chronic asthma. ASM volume increases result from both hypertrophic as well as hyperplastic growth, the latter having been more extensively investigated. There are relatively few in vivo models available for analysis of the underlying mechanism(s) or their regulation by drugs. Human ASM in culture has been used to investigate potential stimuli for ASM proliferation and the signal transduction pathways that subserve these responses. The mitogen-activated protein kinase (MAPK) family members, ERK 1/2 and the phosphoinositol-3-kinase (PI3K) pathways each contribute to the signalling of G1 progression/S-phase entry in ASM. Glucocorticoids and beta(2)-adrenoceptor agonists attenuate, but do not prevent proliferative responses of ASM. Thus, there is scope for improved pharmacological control of this chronic and progressive aspect of asthma pathogenesis.

Adrenergic beta-Agonists↗

PubMed2002

Time course study on the development of allergen-induced airway remodeling in mice: the effect of allergen avoidance on established airway remodeling.

OBJECTIVE AND DESIGN: We carried out a time course study on the development of allergen-induced airway remodeling in a mouse model of allergic asthma. Moreover, we examined the effect of allergen avoidance on the established airway remodeling. MATERIALS AND METHODS: BALB/c mice were sensitized to ovalbumin (OA) with alum, and exposed daily for 3 weeks to aerosolized OA. At each designated point, bronchial responsiveness was measured, and bronchoalveolar lavage and histological examination were carried out. RESULTS: The numbers of inflammatory leukocytes in the airways and the percentage of goblet cells in the epithelium, Th2 cytokine production, IgE production, collagen deposition beneath the basement membrane and bronchial responsiveness to acetylcholine were all markedly increased after repeated antigen challenge for 1-3 weeks. In contrast, after cessation of antigen exposure, goblet cell hyperplasia, inflammatory infiltrates and bronchial hyperresponsiveness were gradually attenuated and had almost resolved 4 weeks after cessation, but subepithelial fibrosis was still observed at this time point. CONCLUSIONS: The present findings demonstrated that epithelial changes following repeated allergen challenge are rapidly induced and recover after the cessation of exposure, but subepithelial fibrosis has a late onset and relatively irreversible changes, and subepithelial fibrosis in contrast to goblet cells hyperplasia did not appear to contribute to bronchial hyperresponsiveness, at least, in this mouse model.

Acetylcholine↗