Extent Of Remodeling Research Articles

Remodeling of Rotational Malunion of Femoral Shaft in Children.

The degree of expected rotational remodeling in femoral shaft fractures is poorly understood, partly because of the difficulty in accurately measuring rotational alignment radiographically before and after treatment. This study aimed to assess the degree of rotational remodeling in the short-term following post-traumatic fracture shaft of the femur with > 10° rotational malunion in children under 15years. We carried out an observational study with a prospective follow-up on 18 children aged < 15years with isolated, unilateral, oblique, or spiral, closed femur shaft fracture treated with closed reduction and immobilization with hip spica or internal fixation with elastic stable intramedullary nails or minimal invasive plate osteosynthesis. Only those with an initial axial malalignment measured on postoperative reduction radiographs of more than 10° by Ozel et al. technique were included. We evaluated the residual rotational malunion outcome using the ultrasound technique of Terjesen et al. by assessing the difference in femoral torsion as a guide to rotational malunion. The difference between the initial malreduction and the torsional difference between the hips at follow-up was deemed the extent of rotational change or remodeling. The mean axial malalignment was 21.6° (10°-32°). The mean rotational remodeling was 13.6° (range 7°-21°), with an SD of 3.9. This study shows that a significant amount of rotational remodeling occurs in children up to 14years of age within 2years of injury. It is higher in younger patients (r = 0.786; p < 0.001), and the extent of remodeling is proportional to the magnitude of the initial deformity (r = 0.81, p < 0.001).

The role of atrial electro-mechanical coupling as predictor of catheter ablation efficiency: EPs and clinicians working together

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) results in electrical and structural remodeling of the atria, and the extent of remodeling has already been found to be associated with higher AF recurrence rate after catheter ablation (CA). Recently, a novel echocardiographic parameter derived from tissue Doppler imaging (TDI), called PA-TDI, has been introduced to assess the total atrial activation time, as a non-invasive surrogate of fibrosis and atrial cardiomyopathy. The aim of the study was to investigate the role of PA-TDI interval as predictor of AF ablation efficacy. Methods Consecutive patients with persistent or paroxysmal symptomatic AF referred to our Center to perform radiofrequency ablation or cryoablation procedures were prospectively enrolled. In these patients, a complete transthoracic echocardiographic examination was performed before and after the ablation procedure, including assessment of the PA-TDI interval. Results From October 2018 to May 2020, 221 consecutive patients (mean age 61 ± 9 years, 74% male, mean BMI 26.5 ± 3.6, mean Ejection Fraction 61 ± 6%) symptomatic for AF, undergoing the procedure ablation (first procedure or re-do) were enrolled. Out of the blanking period, 25% of patients experienced recurrence of arrhythmia during follow-up (mean 16 months). Compared to patients who did not relapse, patients with AF recurrence have a generally longer post-procedural PA-TDI interval (139.6 ± 22.1 msec vs 153.9 ± 33 msec, respectively). In the multivariable analysis only post-procedure PA-TDI and re-do interventions were found to be independent predictors of AF recurrence. A PA-TDI cut-off&amp;gt;144msec identifies patients at risk of post ablation AF recurrence with sensitivity 58.7% and specificity 73.5% (AUC 0.697). Conclusions The PA-TDI interval is an independent predictor of AF recurrence after catheter ablation. This echocardiographic parameter is easily obtainable, low-cost, reproducible, and accessible even in peripheral centers.

C1 THE ROLE OF ATRIAL ELECTRO–MECHANICAL COUPLING AS PREDICTOR OF CATHETER ABLATION EFFICIENCY

Abstract Background Atrial fibrillation (AF) results in electrical and structural remodeling of the atria, and the extent of remodeling has already been found to be associated with higher AF recurrence rate after catheter ablation (CA). Recently, a novel echocardiographic parameter derived from tissue Doppler imaging (TDI), called PA–TDI, has been introduced to assess the total atrial activation time, as a non–invasive surrogate of fibrosis and atrial cardiomyopathy. The aim of the study was to investigate the role of PA–TDI interval as predictor of AF ablation efficacy. Methods Consecutive patients with persistent or paroxysmal symptomatic AF referred to our Center to perform radiofrequency ablation or cryoablation procedures were prospectively enrolled. In these patients, a complete transthoracic echocardiographic examination was performed before and after the ablation procedure, including assessment of the PA–TDI interval. Results From October 2018 to May 2020, 221 consecutive patients (mean age 61 ± 9 years, 74% male, mean BMI 26.5 ± 3.6, mean Ejection Fraction 61 ± 6%) symptomatic for AF, undergoing the procedure ablation (first procedure or re–do) were enrolled. Out of the blanking period, 25% of patients experienced recurrence of arrhythmia during follow–up (mean 16 months). Compared to patients who did not relapse, patients with AF recurrence have a generally longer post–procedural PA–TDI interval (139.6 ± 22.1 msec vs 153.9 ± 33 msec, respectively). In the multivariable analysis only post–procedure PA–TDI and re–do interventions were found to be independent predictors of AF recurrence. A PA–TDI cut–off&amp;gt; 144msec identifies patients at risk of post ablation AF recurrence with sensitivity 58.7% and specificity 73.5% (AUC 0.697). Conclusions The PA–TDI interval is an independent predictor of AF recurrence after catheter ablation. This echocardiographic parameter is easily obtainable, low–cost, reproducible, and accessible even in peripheral centers.

Can the Disoid Meniscus Remodel After Saucerization?

Background/Purpose:The discoid meniscus is a congenital variant that is reported to be present in 3-5% of the United States population. Treatment involves partial meniscectomy and saucerization to obtain a more anatomic-appearing meniscus. The immediate post-operative cross-sectional morphology is often squared due to the inherent thickness of the discoid meniscus at the resection margin. The purpose of this study is to determine if the discoid meniscus can remodel and regain the triangular cross sectional configuration of a normal meniscus after surgical intervention.Methods:A retrospective chart review was performed to identify all patients undergoing partial meniscectomy for symptomatic discoid meniscus within the past 3 years at our institution. Patients were included if they had a subsequent knee magnetic resonance imaging (MRI) study. Each MRI study was evaluated by two orthopaedic surgeons independently. The extent of remodeling was graded on the cross-sectional morphology of the saucerized discoid meniscus on coronal and sagittal T1-weighted images of the corresponding knee mri based on the following scheme: 1) complete for a triangular cross-section, 2) partial for a trapezoidal cross-section , and 3) none for a square cross-section. Descriptive means and statistical analysis for intraclass correlation coefficient (ICC) were performed using Microsoft Excel.Results:A total of 11 patients and 14 knees were included in this study. Average age at time of surgery was 10.85. Average time to the follow-up MRI of the same knee was 540.50 +/- 341.84 days. 2 knees required additional surgical intervention following their index surgery. Complete remodeling was identified in 78.5% (11/14) knees. 1 knee had no remodeling and 2 knees had partial remodeling. Our ICC was 0.87 (95% CI: [0.66,0.96]).Conclusion:Our results indicate that the discoid meniscus has the potential to remodel into a “normal” triangular cross-sectional morphology after partial meniscectomy and saucerization. In our series, 21.4% (3/14) knees did not experience complete remodeling. This may have been due to over resection of the discoid meniscus at the index surgery owing to the extent of an existing tears. The remodeling all occurred within a two-year time frame though the exact time is unknown. This study indicates no additional intervention is required at the central resection margin to thin out the thick edge that often results from the meniscal biter.

Structural remodeling and conduction velocity dynamics in the human left atrium: Relationship with reentrant mechanisms sustaining atrial fibrillation

BackgroundRate-dependent conduction velocity (CV) slowing is associated with atrial fibrillation (AF) initiation and reentrant mechanisms.ObjectiveThe purpose of this study was to assess the relationship between bipolar voltage, CV dynamics, and AF drivers.MethodsPatients undergoing catheter ablation for persistent AF (<24 months) were enrolled. Unipolar electrograms were recorded with a 64-pole basket catheter during atrial pacing at 4 pacing intervals (PIs) during sinus rhythm. CVs were measured between pole pairs along the wavefront path and correlated with underlying bipolar voltage. CV dynamics within low-voltage zones (LVZs <0.5 mV) were compared to those of non-LVZs (≥0.5 mV) and were correlated to driver sites mapped using CARTOFINDER (Biosense Webster).ResultsEighteen patients were included (age 62 ± 10 years). Mean CV at 600 ms was 1.59 ± 0.13 m/s in non-LVZs vs 0.98 ± 0.23 m/s in LVZs (P <.001). CV decreased incrementally over all 4 PIs in LVZs, whereas in non-LVZs a substantial decrease in CV was only seen between PIs 300–250 ms (0.59 ± 0.09 m/s; P <.001). Rate-dependent CV slowing sites measurements, defined as exhibiting CV reduction ≥20% more than the mean CV reduction seen between PIs 600–250 ms for that voltage zone, were predominantly in LVZs (0.2–0.5 mV; 75.6% ± 15.5%; P <.001). Confirmed rotational drivers were mapped to these sites in 94.1% of cases (sensitivity 94.1%, 95% CI 71.3%–99.9%; specificity 77.9%, 95% CI 74.9%–80.7%).ConclusionCV dynamics are determined largely by the extent of remodeling. Rate-dependent CV slowing sites are predominantly confined to LVZs (0.2–0.5 mV), and the resultant CV heterogeneity may promote driver formation in AF.

Functional genioplasty in growing patients

Objective - To evaluate the role of age as a moderator of bone regeneration patterns and symphysis remodeling after genioplasty. Method - Fifty-four patients who underwent genioplasty at the end of their orthodontic treatment were divided into three age groups: younger than 15 years at the time of surgery (group 1), 15 to 19 years (group 2), and 20 years or older (group 3). Twenty-three patients who did not accept genioplasty and had a follow-up radiograph two years after the end of their orthodontic treatment were used as a control group. Patients were evaluated at three time points: immediate preoperative (T1), immediate postoperative (T2) and two years postsurgery (T3). Results - The mean genial advancement at surgery was similar for the three age groups, but the extent of remodeling around the repositioned chin was greater in group 1, less in group 2, and still less in group 3. Symphysis thickness increased significantly during the two-years postsurgery interval for the three groups, and this increase was significantly greater in group 1 than in group 3. Remodeling above and behind the repositioned chin also was greater in the younger patients. This was related to greater vertical growth of the dentoalveolar process in the younger patients. There was no evidence of a deleterious effect on mandibular growth. Conclusion - The outcomes of forward-upward genioplasty include increased symphysis thickness, bone apposition above B point, and remodeling at the inferior border. When indications for this type of genioplasty are recognized, early surgical correction (before age 15) produces a better outcome in terms of bone remodeling.

Functional genioplasty in growing patients.

To evaluate the role of age as a moderator of bone regeneration patterns and symphysis remodeling after genioplasty. Fifty-four patients who underwent genioplasty at the end of their orthodontic treatment were divided into three age groups: younger than 15 years at the time of surgery (group 1), 15 to 19 years (group 2), and 20 years or older (group 3). Twenty-three patients who did not accept genioplasty and had a follow-up radiograph 2 years after the end of their orthodontic treatment were used as a control group. Patients were evaluated at three time points: immediate preoperative (T1), immediate postoperative (T2,) and 2 years postsurgery (T3). The mean genial advancement at surgery was similar for the three age groups, but the extent of remodeling around the repositioned chin was greater in group 1, less in group 2, and still less in group 3. Symphysis thickness increased significantly during the 2-year postsurgery interval for the three groups, and this increase was significantly greater in group 1 than in group 3. Remodeling above and behind the repositioned chin also was greater in the younger patients. This was related to greater vertical growth of the dentoalveolar process in the younger patients. There was no evidence of a deleterious effect on mandibular growth. The outcomes of forward-upward genioplasty include increased symphysis thickness, bone apposition above B point, and remodeling at the inferior border. When indications for this type of genioplasty are recognized, early surgical correction (before age 15) produces a better outcome in terms of bone remodeling.

Remodeling of the Postsynaptic Density: A Macromolecular Signaling Complex

The postsynaptic density (PSD), a macromolecular protein machine that resides under the postsynaptic plasma membrane, regulates the efficiency of synaptic transmission by stabilizing neurotransmitter receptors in the membrane and organizing signaling molecules within the postsynaptic compartment. Data suggests that synaptic activity results in changes in the protein composition of the PSD and it is hypothesized that these changes lead to structural modifications that explain enduring and stable alterations in synaptic function. However, direct evidence for these structural changes has never been obtained and the extent of remodeling and the mechanisms responsible are not fully understood. Our long term goal is to create a high-resolution molecular model of the PSD that accurately represents the number and 3D relationships between its protein components allowing hypothesis to be generated about how recruitment or loss of specific proteins results in structural alterations at the PSD. The ubiquitin proteasome system (UPS) targets proteins for degradation and is, in part, responsible for modifications of the proteins that compose the PSD. Synaptic activity has been shown to induce proteasomal recruitment into the postsynaptic compartment, that requires prior activity-dependent recruitment of CaMKII, resulting in changes in protein composition of PSDs. Electron cryo-tomography (ECT) and immunogold labeling were employed to examine the 3D structure of isolated PSDs and to identify scaffold molecules targeted by the UPS. Proteasome levels were found to be highest in PSDs isolated earlier in development, providing evidence that the UPS plays a crucial role in the structural reorganization of PSDs. ECT will also be utilized to examine whether CaMKII functions as a direct scaffold for the proteasome that might serve as a mechanism to spatially restrict protein degradation.

Tooth loss and alveolar remodeling in Sinosaurus triassicus (Dinosauria: Theropoda) from the lower jurassic strata of the Lufeng Basin, China

Pathological or traumatic loss of teeth often results in the resorption and remodeling of the affected alveoli in mammals. However, instances of alveolar remodeling in reptiles are rare. A remodeled alveolus in the maxilla of the Chinese theropod Sinosaurus (Lower Jurassic Lower Lufeng Formation) is the first confirmed example of such dental pathology in a dinosaur. Given the known relationship between feeding behavior and tooth damage in theropods (teeth with spalled enamel, tooth crowns embedded in bone) and the absence of dentary, maxillary, and premaxillary osteomyelitis, traumatic loss of a tooth is most likely the cause of alveolar remodeling. Based on the extent of remodeling, the injury and subsequent tooth loss were non-fatal in this individual.

Yeast cells accumulate excess endogenous palmitate in phosphatidylcholine by acyl chain remodeling involving the phospholipase B Plb1p

In the yeast Saccharomyces cerevisiae, the molecular species profile of the major membrane glycerophospholipid phosphatidylcholine (PC) is determined by the molecular species-selectivity of the biosynthesis routes and by acyl chain remodeling. Overexpression of the glycerol-3-phosphate acyltransferase Sct1p was recently shown to induce a strong increase in the cellular content of palmitate (C16:0). Using stable isotope labeling and mass spectrometry, the present study shows that wild type yeast overexpressing Sct1p incorporates excess C16:0 into PC via the methylation of PE, the CDP-choline route, and post-synthetic acyl chain remodeling. Overexpression of Sct1p increased the extent of remodeling of PE-derived PC, providing a novel tool to perform mechanistic studies on PC acyl chain exchange. The exchange of acyl chains occurred at both the sn-1 and sn-2 positions of the glycerol backbone of PC, and required the phospholipase B Plb1p for optimal efficiency. Sct1p-catalyzed acyl chain exchange, the acyl-CoA binding protein Acb1p, the Plb1p homologue Plb2p, and the glycerophospholipid:triacylglycerol transacylase Lro1p were not required for PC remodeling. The results indicate that PC serves as a buffer for excess cellular C16:0.

MRI-based prediction of adverse cardiac remodeling after murine myocardial infarction

Myocardial infarction (MI) results in adverse cardiac remodeling leading to heart failure and increased mortality. Experimental mouse models of MI are extensively used to identify mechanisms underlying adverse remodeling, but the extent of remodeling that occurs may be highly variable and can limit the utility to discover new disease pathways. The ability to predict the development of significant late post-MI remodeling would be invaluable in conducting such studies by increasing throughput and efficiency. This study aimed to identify potential thresholds of cardiac magnetic resonance imaging (MRI) parameters measured early after murine MI that would predict the development of significant adverse remodeling at 4 wk. MI was achieved by permanent coronary ligation and animals (n = 84) were followed up for 4 wk subsequently. MRI was used to assess left ventricular (LV) volumes, mass and ejection fraction, as well as infarct size (IS). Late gadolinium enhancement cine-MRI was performed at 2 days with standard cine-MRI at 30 days post-MI. Utilizing multiple logistic regression, we found that IS >36%, at 2 days post-MI, was the overall best single predictor of adverse remodeling at 30 days (sensitivity 80.7%, specificity 88.9%; C-statistic of 0.939 from receiver-operating curve analysis). LV end-systolic volume (LVESV) >32 μl was also an excellent predictor comparable to IS. The combination of IS >36% and/or LVESV >32 μl provided the highest predictive values for late adverse remodeling among multiple predictors. This study demonstrates that MRI-based estimation of IS and ESV during the acute phase of murine MI are good predictors of subsequent adverse remodeling that may aid experimental design.

Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction

BackgroundPrediction of left ventricular (LV) remodeling after acute myocardial infarction (MI) is clinically important and would benefit from the discovery of new biomarkers.MethodsBlood samples were obtained upon admission in patients with acute ST-elevation MI who underwent primary percutaneous coronary intervention. Messenger RNA was extracted from whole blood cells. LV function was evaluated by echocardiography at 4-months.ResultsIn a test cohort of 32 MI patients, integrated analysis of microarrays with a network of protein-protein interactions identified subgroups of genes which predicted LV dysfunction (ejection fraction ≤ 40%) with areas under the receiver operating characteristic curve (AUC) above 0.80. Candidate genes included transforming growth factor beta receptor 1 (TGFBR1). In a validation cohort of 115 MI patients, TGBFR1 was up-regulated in patients with LV dysfunction (P < 0.001) and was associated with LV function at 4-months (P = 0.003). TGFBR1 predicted LV function with an AUC of 0.72, while peak levels of troponin T (TnT) provided an AUC of 0.64. Adding TGFBR1 to the prediction of TnT resulted in a net reclassification index of 8.2%. When added to a mixed clinical model including age, gender and time to reperfusion, TGFBR1 reclassified 17.7% of misclassified patients. TGFB1, the ligand of TGFBR1, was also up-regulated in patients with LV dysfunction (P = 0.004), was associated with LV function (P = 0.006), and provided an AUC of 0.66. In the rat MI model induced by permanent coronary ligation, the TGFB1-TGFBR1 axis was activated in the heart and correlated with the extent of remodeling at 2 months.ConclusionsWe identified TGFBR1 as a new candidate prognostic biomarker after acute MI.

Regional cardiac dysfunction is associated with specific alterations in inflammatory cytokines and matrix metalloproteinases after acute myocardial infarction in sheep

Cardiac remodeling following myocardial infarction (MI) is a maladaptive process, fundamental to the progression of ischemic heart failure. The extent of remodeling is influenced by mechanical stress, inflammatory response and activation of matrix metalloproteinases (MMPs). This study examined regional association between these parameters in response to acute MI. Coronary ligation was performed in ten sheep. Sonomicrometer transducers measured segmental length in the infarcted, border and non-infarcted region. Regional tissue samples obtained 3 h post MI from six sheep were analysed using RT-PCR, gelatin zymography and Western blot. Six sham-operated sheep served as controls.Region-specific dilation and reduced contraction was associated with corresponding alterations in matrix molecules.IL-6 and MMP-9 mRNA were increased in the infarcted and border regions compared to controls.MMP-2 and TIMP-1 mRNA increased in non-infarcted myocardium and both correlated positively with segmental shortening. IL-6 mRNA levels, in contrast, were negatively associated with segmental shortening. In summary, inflammatory cytokines and MMPs are altered early after MI in a region-specific manner, and these changes correspond to acute regional myocardial dysfunction. Therapies for LV remodeling from the time of reperfusion may benefit from further understanding this portfolio of acute alterations.

The boundary of macaque rDNA is constituted by low-copy sequences conserved during evolution

In Macaca mulatta, the single rDNA array is flanked by a patchwork of sequences including subregions of human Yp11.2, 4q35.2, and 10p15.3. This composite DNA region is characterized by unique or low-copy sequences, resembling a potentially transcribed region. The analysis of Cercopithecus aethiops, Presbytis cristata, and Hylobates lar suggests that this complex sequence organization could be shared by Old World monkey and lesser ape species. After the lesser apes/great apes divergence, the unique or nonduplicated DNA region underwent amplification and spreading, preferentially marking the p arm of acrocentric chromosomes bearing the rDNA. The molecular analysis of human acrocentric chromosomes revealed some extent of remodeling of the rDNA boundary: near the human NOR, a large 4q35.2 duplication partially resembles that found in MMU; conversely, infrequently represented Yp11.2 sequences totally differed from those of the macaque, and 10p15.3 sequences were lacking. Thus, although evolutionary events modified the sequence organization of the MMU rDNA boundary, its overall sequence feature and the preferential location in vicinity to the NOR have been conserved.

Plasminogen Activator Expression Correlates with Genetic Differences in Vascular Remodeling

Intima-media thickening (IMT) of the carotid artery, a form of vascular remodeling, correlates well with coronary artery disease risk in humans. Vascular remodeling in response to blood flow is a complex process that critically involves altered cell matrix interactions. To gain insight into these events, we performed partial carotid ligation (left carotid (LCA) = low flow and right carotid (RCA) = high flow) in 2 inbred mouse strains: C57Bl/6J (C57) and FVB/NJ (FVB). To evaluate the role of the 2 major matrix-degrading systems, plasminogen activators (PAs) and matrix metalloproteinases (MMPs), we compared the expression of u-PA, t-PA, MMP-2 and MMP-9 in ligated carotids of C57 and FVB mice. The extent of remodeling was greater in response to low LCA than high RCA flow. Despite a similar decrease in LCA flow in both strains, maximal IMT volume was greater in FVB (82 ± 7 × 10^–6 µm³) than in C57 (38 ± 4 × 10^–6 µm³) after ligation. Among PAs and MMPs, increased expression of t-PA and u-PA correlated with increased IMT (p < 0.0005 and p < 0.001, respectively). MMP-2, MMP-9 and tissue inhibitors of metalloproteinase-2 expression also increased, but did not differ between strains. In summary, flow-induced IMT of the carotid is genetically determined and correlates with t-PA and u-PA expression in 2 inbred mouse strains.

Extra-stent vascular remodeling in in-stent restenosis after 188Re-MAG 3 radiation therapy

Background: The effect of β-radiation on extra-stent vascular remodeling in patients with in-stent restenosis has not been studied. The correlation between the extent of extra-stent plaque proliferation and that of intimal hyperplasia (IH) in in-stent restenosis in patients who received β-radiation therapy as well as conventional therapy has also not been studied. Methods: We evaluated the extra-stent remodeling in diffuse in-stent restenosis between a β-radiation therapy patient group ( 188Re-MAG 3, n=50) and a control group ( n=9) by applying serial intravascular ultrasound (IVUS) analysis. Matching (post-intervention and follow-up) images were acquired at the follow-up lesion site and were available in 44 of 50 patients who received radiation therapy and in seven of nine control patients. Results: There was a significant increase of the external elastic membrane (EEM) area in both groups: 16.4±3.3 mm 2 post-intervention to 17.1±3.3 mm 2 at follow-up, P=0.001 in the radiation therapy group, and 16.8±4.0 mm 2 post-intervention to 17.4±4.1 mm 2 at follow-up, P=0.008 in the control group. There were no statistically significant differences of the Δ EEM area between the two groups: 0.7±0.4 mm 2 in the radiation therapy group vs. 0.6±0.4 mm 2 in the control group, P=0.389. The Δ IH area correlated with the Δ EEM area in the control group ( r=0.826, P=0.022), but not in the radiation therapy group ( r=0.016, P=0.919). Conclusions: The findings of this IVUS study were that positive remodeling (increased EEM area) occurred equally in both control and irradiated patients with in-stent restenosis. The extent of remodeling was directly in proportion to IH in the control group, but no such relationship existed in the irradiated patient group.

Importance of an intact growth hormone/insulin-like growth factor 1 axis for normal post-infarction healing: studies in dwarf rats.

Treatment with GH attenuates remodeling and improves left ventricular function in the setting of experimental heart failure following coronary ligation. This study was designed to test the hypothesis that an intact GH/insulin-like growth factor 1 (IGF-1) axis is required for normal myocardial infarction healing. Myocardial infarction was induced by coronary ligation in GH-deficient dwarf rats and in age-matched controls. In dwarf rats, serum IGF-1 levels were reduced by 50%, and grow rate was 50% less than normal littermates, although no differences in myocardial IGF-1 messenger RNA levels were observed compared with controls. All rats underwent transthoracic echocardiography at baseline, 2 weeks, and 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure was obtained by in vivo closed chest catheterization. At 6 weeks, both infarcted groups exhibited similar myocardial infarction size at transthoracic echocardiography and at morphometric histology. In both groups with myocardial infarction, there was significant left ventricular dilation and reduced systolic function. However, the extent of remodeling as assessed by the increase in end-diastolic dimension (%Delta + 36 +/- 5 vs. +19 +/- 4; P: < 0.01) and depression of function (%Delta fractional shortening -12 +/- 2 vs. -7 +/- 1; P: < 0.01) were both greater in the dwarf group. Furthermore, dwarf rats failed to develop compensatory hypertrophy of noninfarcted posterior wall (%Delta posterior wall +5 +/- 1 vs. +15 +/- 3; P: < 0.01). Therefore, pathologic left ventricular remodeling and functional loss following myocardial infarction is more marked in conditions of GH deficiency. An intact GH/IGF-1 axis appears necessary for a normal response to myocardial infarction injury in the rat.

Transcriptional Regulation of the Yeast PHO8 Promoter in Comparison to the Coregulated PHO5 Promoter

Expression of the PHO8 and PHO5 genes that encode a nonspecific alkaline and acid phosphatase, respectively, is regulated in response to the P(i) concentration in the medium by the same transcription factors. Upon induction by phosphate starvation, both promoters undergo characteristic chromatin remodeling, yet the extent of remodeling at the PHO8 promoter is significantly lower than at PHO5. Despite the coordinate regulation of the two promoters, the PHO8 promoter is almost 10 times weaker than PHO5. Here we show that of two Pho4 binding sites that had been previously mapped at the PHO8 promoter in vitro, only the high affinity one, UASp2, is functional in vivo. Activation of the PHO8 promoter is partially Pho2-dependent. However, unlike at PHO5, Pho4 can bind strongly to its binding site in the absence of Pho2 and remodel chromatin in a Pho2-independent manner. Replacement of the inactive UASp1 element by the UASp1 element from the PHO5 promoter results in more extensive chromatin remodeling and a concomitant 2-fold increase in promoter activity. In contrast, replacement of the high affinity UASp2 site with the corresponding site from PHO5 precludes chromatin remodeling completely and as a consequence promoter activation, despite efficient binding of Pho4 to this site. Deletion of the promoter region normally covered by nucleosomes -3 and -2 results in a 2-fold increase in promoter activity, further supporting a repressive role of these nucleosomes. These data show that there can be strong binding of Pho4 to a UAS element without any chromatin remodeling and promoter activation. The close correlation between promoter activity and the extent of chromatin disruption strongly suggests that the low level of PHO8 induction in comparison with PHO5 is partly due to the inability of Pho4 to achieve complete chromatin remodeling at this promoter.

Extent and direction of arterial remodeling in stable versus unstable coronary syndromes : an intravascular ultrasound study.

The morphological characteristics of coronary plaques in patients with stable versus unstable coronary syndromes have been described in vivo with intravascular ultrasound, but the relationship between arterial remodeling and clinical presentation is not well known. We studied 85 patients with unstable and 46 patients with stable coronary syndromes using intravascular ultrasound before coronary intervention. The lesion site and a proximal reference site were analyzed. The remodeling ratio (RR) was defined as the ratio of the external elastic membrane (EEM) area at the lesion to that at the proximal reference site. Positive remodeling was defined as an RR >1.05 and negative remodeling as an RR <0.95. Plaque area (13.9+/-5.5 versus 11.1+/-4.8 mm(2); P=0.005), EEM area (16.1+/-6.2 versus 13.0+/-4.8 mm(2); P=0. 004), and the RR (1.06+/-0.2 versus 0.94+/-0.2; P=0.008) were significantly greater at target lesions in patients with unstable syndromes than in patients with stable syndromes. Positive remodeling was more frequent in unstable than in stable lesions (51. 8% versus 19.6%), whereas negative remodeling was more frequent in stable lesions (56.5% versus 31.8%) (P=0.001). Positive remodeling and larger plaque areas were associated with unstable clinical presentation, whereas negative remodeling was more common in patients with stable clinical presentation. This association between the extent of remodeling and clinical presentation may reflect a greater tendency of plaques with positive remodeling to cause unstable coronary syndromes.

Type and extent of vascular remodeling in significant coronary lesions: An intravascular ultrasound study

The purpose of this study was to assess the dimension of regional vascular remodeling and its influence on lumen narrowing in vivo. Sixty-three patients with 68 coronary lesions were imaged by intravascular ultrasound before transcatheter therapy. Quantitative measurements of lumen area, vessel area, and plaque area were performed at the lesion site and at the proximal and distal reference site. Area stenosis was calculated as plaque area/vessel area. 100. The extent of remodeling was quantified by a remodeling index (RI = stenosis vessel area - mean reference vessel area/mean reference vessel area. 100). Additionally, three different groups of vascular remodeling were defined: 1) positive remodeling = stenosis vessel area > maximal reference vessel area; 2) intermediate remodeling = maximal reference vessel area >/= stenosis vessel area >/= minimal reference vessel area; 3) negative remodeling = stenosis vessel area < minimal reference vessel area. In 57% of lesions stenosis vessel area was not in between the proximal and distal reference area: 29% of lesions (20/68) had positive, 28% (19/68) negative, and 43% (29/68) intermediate remodeling. Overall remodeling index averaged -0.8+/-19.7%. In the negative remodeling group, reduction of vessel area contributed to 40+/-21% of lumen narrowing, in the positive remodeling group, stenosis vessel area was 21+/-12% enlarged (p<0.001). Lesions with negative remodeling exhibit a lesser plaque area, lesions with positive remodeling a larger than other vessels (8.2+/-2.4 mm(2), 13.8+/-3.7 mm(2), 10. 8+/-3.7 mm(2); p <0.001). Distinct vascular remodeling occurred in the majority of atherosclerotic lesions and is a bidirectional process. Overall, the extent and the frequency of positive and negative remodeling was almost balanced. In lesions with negative remodeling the plaque area was significantly lesser than in other lesions.