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PubMed2003

Relative contributions of intimal hyperplasia and vascular remodeling in early cardiac transplant-mediated coronary artery disease.

The relative contribution of intimal hyperplasia and vascular remodeling in early transplant coronary artery disease (TxCAD) is unknown. This study was designed to determine the contributions of vascular remodeling and intimal hyperplasia in the initial year after transplantation by intravascular ultrasound (IVUS). Twenty-five patients underwent baseline (<6 weeks after transplant) and 1-year angiography and IVUS to evaluate total vessel, luminal, and intimal + medial areas in >or=3 segments of the coronary artery. Nine patients had donor atherosclerotic disease on baseline study (23% of segments), and at 1-year, 21 patients (84%) had intimal hyperplasia (70% of segments). Fourteen patients had positive remodeling in all arterial segments, whereas the remaining 11 had positive and negative remodeling in the same vessel. Mean plaque area and total vessel area increased significantly (p = 0.0001) in proximal, mid, and distal segments, whereas total vessel area was most pronounced in distal segments. Luminal area did not change over time. Of the 87 segments evaluated, 68 (78%) had an increase in total vessel area, 57 (66%) had intimal growth, and 54 (62%) had an increase in luminal area. Although changes in total vessel and luminal area were closely correlated, a decrease in luminal area was associated with positive and negative remodeling. In conclusion, luminal area is generally maintained during the initial transplant year despite significant intimal hyperplasia due to positive remodeling. Reduction in the luminal area results from either inadequate positive remodeling or negative remodeling without intimal growth and often occurs in the same artery.

Adult↗

PubMed2002

Heart failure in pressure overload hypertrophy. The relative roles of ventricular remodeling and myocardial dysfunction.

OBJECTIVES: We sought to explore the relative contributions of ventricular remodeling and myocardial dysfunction to heart failure in pressure overload hypertrophy (POH). BACKGROUND: The mechanism that underlies heart failure in POH is adverse left ventricular (LV) chamber remodeling or decreased myocardial function, or a combination of these. METHODS: Twenty weeks after suprarenal aortic banding in rats, animals with POH were classified as those with heart failure (POH-HF) or those with no heart failure (POH-NHF). The LV chamber and myocardial systolic and diastolic functions were determined from in vivo and ex vivo experiments. RESULTS: The LV mass was similar in both POH groups. Chamber remodeling in the POH-HF group was characterized by marked LV enlargement with a normal relative wall thickness (eccentric remodeling), whereas remodeling in the POH-NHF group was characterized by a normal chamber size and increased relative wall thickness (concentric remodeling). The LV systolic function, as determined in vivo from the end-systolic pressure-diameter relationship and ex vivo from the pressure-volume relationship, was lower in the POH-HF group than in the POH-NHF and sham-operated control groups. In contrast, myocardial function was similar in both POH groups, as determined in vivo from the stress-midwall fractional shortening relationship and myocardial systolic stiffness, and ex vivo from the slope of the LV systolic stress-strain relationship. The diastolic chamber stiffness constant was lower in the POH-HF group than in the POH-NHF group, but the myocardial stiffness constant was similar in the two POH groups. CONCLUSIONS: The two POH groups differed primarily in their remodeling process, which led to a chronically compensated state in one group and to heart failure in the other. Hence, heart failure in POH is more closely related to deleterious LV remodeling than to depressed myocardial function.

Animals↗

PubMed1999

Temporomandibular joint remodeling in adolescents and young adults during Herbst treatment: A prospective longitudinal magnetic resonance imaging and cephalometric radiographic investigation.

The aim of this prospective study was to analyze and compare the temporomandibular joint adaptive mechanisms in 25 adolescent and 14 young adult Class II malocclusions treated with the Herbst appliance. Temporomandibular joint remodeling was analyzed by magnetic resonance imaging. In each subject, 4 magnetic resonance images of both temporomandibular joints were available: before treatment, at the start of treatment (when the Herbst appliance was placed), during treatment (6 to 12 weeks after appliance placement), and after treatment (when the appliance was removed). Furthermore, effective temporomandibular joint changes (the sum of condylar remodeling, fossa remodeling, and condyle-fossa relationship changes) were analyzed with the aid of lateral cephalometric radiographs from before and after treatment. All subjects were treated to Class I or overcorrected Class I dental arch relationships, and their mandibles became significantly (P <.001) more prognathic. After 6 to 12 weeks of Herbst treatment, signs of condylar remodeling were seen at the posterosuperior border in 48 of the 50 adolescent condyles and in 26 of the 28 young adult condyles. Bilateral remodeling of the mandibular ramus could be detected in 1 adolescent and 2 young adult patients. Signs of glenoid fossa remodeling at the anterior surface of the postglenoid spine were noted in 36 adolescent and 22 young adult temporomandibular joints. Effective temporomandibular joint changes during treatment were more horizontally directed and larger in both adolescents and young adult patients treated with the Herbst appliance than in an untreated group of subjects with ideal occlusion (Bolton standards). The increase in mandibular prognathism accomplished by Herbst therapy in both adolescents and young adults seems, in particular, to be a result of condylar and glenoid fossa remodeling. Because the Herbst appliance is most successful in Class II patients also at the end of the growth period, the treatment method could be an alternative to orthognathic surgery in borderline skeletal Class II cases. Magnetic resonance imaging renders an excellent opportunity to visualize the temporomandibular joint remodeling growth processes.

Adaptation, Physiological↗

PubMed2001

A theoretical analysis of the contributions of remodeling space, mineralization, and bone balance to changes in bone mineral density during alendronate treatment.

In patients with osteoporosis, alendronate treatment causes an increase in bone mineral density (BMD) and a decrease in fracture incidence. Alendronate acts by changing the bone remodeling process. Changes in bone remodeling resulting in decreased remodeling space, increased bone balance per remodeling cycle, and increased mineralization (ash mass/bone mass) have all been associated with alendronate treatment. Understanding the relative contributions of these parameters to BMD increases could help predict the utility of long-term (>10 years) or intermittent treatment strategies, as well as treatment strategies in which another pharmaceutical is administered concurrently. We have developed a computer simulation of bone remodeling to compare the contributions of focal bone balance and mineralization on BMD by simulating alendronate treatment using a bone balance method (decreased remodeling space, increased focal bone balance, uniform bone mineralization) and a mineralization method (decreased remodeling space, neutral focal bone balance, varying bone mineralization). Although both methods are able to predict BMD increases caused by alendronate over short periods, our findings suggest that the mineralization method may be more descriptive of long-term alendronate treatment. This implies that mineralization may be a larger contributor to BMD changes caused by alendronate than the focal bone balance. Based on this finding we offer a hypothesis to describe how remodeling space, focal bone balance, and mineralization each contribute to alendronate-induced BMD changes. Future analyses with this method could be used to identify improved dosing regimens and to predict which osteoporosis treatments would best complement each other.

Alendronate↗

PubMed2002

Is all cortical bone remodeling initiated by microdamage?

There is increasing interest in the degree to which bone remodeling, particularly in cortical bone, is "targeted" at fatigue microdamage. The theory that microdamage initiates remodeling in close proximity to microcracks, thereby removing them, and that this accounts for a significant fraction of the overall remodeling activity, has been gaining acceptance. However, the association between the initial, resorptive stage of remodeling and microcracks in histologic sections of cortical bone is far from complete; indeed, the great majority of resorption spaces are not spatially associated with microcracks. This observation has maintained support for the older concept that most remodeling occurs primarily for such metabolic purposes as calcium homeostasis. To gain further insight regarding the degree to which microdamage governs remodeling, this study presents a mathematical analysis based on the unorthodox hypothesis that all cortical bone remodeling is initiated by, and in close proximity to, microcracks. Equations are derived showing that, because remodeling basic multicellular units (BMUs) travel several millimeters beyond their point of initiation, the relative numbers of resorption spaces and microcracks found in close spatial proximity or isolated from one another are consistent with the hypothesis. The results also predict the degree to which the spatial association between resorption spaces and microcracks should exceed that due to chance alone. There are as yet very limited experimental data suitable for testing this model, but the existing data closely correspond to the model's predictions.

Animals↗

PubMed2003

Interruption of signal transduction between G protein and PKC-epsilon underlies the impaired myocardial response to ischemic preconditioning in postinfarct remodeled hearts.

We have recently shown that the protective mechanism of ischemic preconditioning (PC) is impaired in the myocardium that survived infarction and underwent postinfarct ventricular remodeling. In this study, we examined the hypothesis that failure of PC to activate PKC-epsilon underlies the refractoriness of the remodeling heart to PC. Circumflex coronary arteries were ligated in rabbits to induce infarction and subsequent ventricular remodeling, and only sham operations were performed in controls. Hearts were isolated before (i.e. 4 days later) or after (i.e. 2 weeks later) remodeling of the left ventricle and used for isolated buffer-perfused heart experiments. Myocardial infarction was induced in isolated hearts by 30 min global ischemia/2 h reperfusion, and its size was measured by tetrazolium staining. Using separate groups of hearts, tissue biopsies were taken before and after PC, and PKC translocation was assessed by Western blotting. Areas infarcted in vivo by coronary ligation (CL) were excluded from subsequent infarct size/PKC analyses. In the hearts 4 days after CL, PC with 2 cycles of 5 min ischemia/5 min reperfusion induced PKC-epsilon translocation from cytosol to particulate fractions and limited infarct size to 40% of control value. In the hearts remodeled 2 weeks after CL, PC failed to induce PKC-epsilon translocation and infarct size limitation. In this group, PKC activity and hemodynamic responses to adenosine were similar to those in sham-operated controls. When remodeling after CL was prevented by valsartan infusion (10 mg/kg/day), an angiotensin II type 1 (AT1) receptor blocker, PC could induce both infarct limitation and PKC-epsilon translocation. The present results suggest that persistent activation of AT1 receptors during remodeling disturbed the PC signaling between G proteins and PKC-epsilon, which underlies the refractoriness of the remodeled myocardium to PC.

Adenosine↗

PubMed2000

Cardioprotective mechanism of ischemic preconditioning is impaired by postinfarct ventricular remodeling through angiotensin II type 1 receptor activation.

BACKGROUND: Activation of protein kinase C-linked receptors and subsequent opening of the mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel are crucial in preconditioning (PC). This study examined whether postinfarct ventricular remodeling interferes with the PC mechanism. METHODS AND RESULTS: Two weeks before isolation of hearts, rabbits underwent a sham operation or coronary ligation (COL) to induce remodeling. Isolated buffer-perfused hearts were subjected to 30-minute global ischemia/2-hour reperfusion, and infarct size was expressed as a percentage of the left ventricle (%I/LV), from which the scarred infarct by COL was excluded. Although %I/LV was similar in sham-operated and remodeled hearts (52.9+/-6.5% versus 45.8+/-5.2%), PC with 2 episodes of 5-minute ischemia protected sham-operated but not remodeled hearts (%I/LV=18.1+/-2.5% versus 54.8+/-2.9%, P<0.05). Infusion of valsartan (10 mg x kg(-1). d(-1), an angiotensin II type 1 (AT(1)) receptor blocker, for 2 weeks after COL prevented the ventricular remodeling and preserved the response to PC (%I/LV=27.4+/-3.8%), although valsartan alone did not change %I/LV. Diazoxide, a mitoK(ATP) channel opener, protected both sham-operated and remodeled hearts (%I/LV=14.1+/-3.1% and 8.3+/-3.6%). CONCLUSIONS: The myocardium remodeled after infarction is refractory to PC, which is probably due to interruption of cellular signaling by PC upstream of mitoK(ATP) channels. An AT(1) receptor blocker is beneficial not only for suppression of ventricular remodeling but also for preservation of the PC mechanism.

Angiotensin II↗

PubMed2001

Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers.

We describe a sinus, referred to as a bone remodeling compartment (BRC), which is intimately associated with cancellous bone remodeling. The compartment is lined on its marrow side by flattened cells and on its osseous side by the remodeling bone surface, resembling a roof of flattened cells covering the bone surface. The flat marrow lining cells are in continuity with the bone lining cells at the margins of the BRC. We examined a large number of diagnostic bone biopsy specimens received during recent years in the department. Furthermore, 10 patients (8 women and 2 men, median age 56 [40-69] years) with the high turnover disease of primary hyperparathyroidism who were treated with parathyroidectomy and followed for 3 years were included in the histomorphometric study. Bone samples for the immuno-enzyme staining were obtained from an amputated extremity of child. The total cancellous bone surface covered by BRC decreases by 50% (p < 0.05) following normalization of turnover and is paralleled by a similar 50% decrease in remodeling surface (p < 0.05). The entire eroded surface and two-thirds of the osteoid surface are covered by a BRC. BRC-covered uncompleted walls are 30% (p < 0.05) thinner than those without a BRC. This indicates that the BRC is invariably associated with the early phases of bone remodeling, that is, bone resorption, whereas it closes during the late part of bone formation. Immuno-enzyme staining shows that the flat marrow lining cells are positive for alkaline phosphatase, osteocalcin, and osteonectin, suggesting that they are bone cells. The first step in cancellous bone remodeling is thought to be the lining cells digesting the unmineralized matrix membrane followed by their disappearance and the arrival of the bone multicellular unit (BMU). We suggest that the lining cell barrier persists during bone remodeling; that the old lining cells become the marrow lining cells, allowing bone resorption and bone formation to proceed under a common roof of lining cells; that, at the end of bone formation, new bone lining cells derived from the flattened osteoblasts replace the marrow lining cells thereby closing the BRC; and that the two layers of lining cells eventually becomes a single layer. The integrity of the osteocyte-lining cell system is reestablished by the new generation of lining cells. The BRC most likely serves multiple purposes, including efficient exchange of matrix constituents and minerals, routing, monitoring, or modulating bone cell recruitment, and possibly the anatomical basis for the coupling of bone remodeling.

Adult↗

PubMed2003

Changes and significance of subtype function of beta-adrenoreceptors in left ventricular remodeling of hypertension.

Changes in the density of myocardium and blood lymphocyte beta-adrenoceptors (beta-AR) in left ventricular (LV) geometry have been found in patients with essential hypertension (EH). However, it is not known whether intrinsic beta-AR subtype function changes during left ventricular remodeling of hypertension. The purpose of this study was to further investigate the changes and clinical significance of beta-AR subtype function in LV remodeling in patients with EH. One hundred and thirty-four men (mean age, 53 years) with EH as defined in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure grades 1 to 2 and 40 normotensives were studied. Based on the echocardiographic LV mass index and relative wall thickness, four patterns of LV geometry, ie, normal left ventricle, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy were identilied. beta-Adrenoreceptor subtype responsiveness was measured by a treadmill exercise test (to measure cardiac beta1-adrenoreceptor responsiveness) and by Salbutamol injection test (to measure cardiac beta2-adrenoreceptor responsiveness) in 134 male patients with EH. Forty normotension subjects were also studied as controls. In patients with EH in the groups of concentric remodeling, concentric hypertrophy, and eccentric hypertrophy, heart rate in response to the treadmill test (peak exercise-resting rate) was significantly higher (P < 0.05, P < 0.01. P < 0.01, respectively) than that in the control group. In the concentric remodeling and concentric hypertrophy group, the chronotropic doses of salbutamol required to increase the heart rate by 30 beats/min (CD30) were significantly lower (P < 0.05, P < 0.01, respectively) than that in the control group. However, in the eccentric hypertrophy group. CD30 was higher significantly (P < 0.01) than that in the control group. In the concentric remodeling, concentric hypertrophy, and eccentric hypertrophy groups, beta1-AR responsiveness significantly increased them in the normotensive group, whereas beta2-AR responsiveness significantly increased in the concentric remodeling and concentric hypertrophy groups them in the normotensive group, and significantly decreased in the eccentric hypertrophy them in the normotensive group. The results suggest that non-beta-selective blocker may be beneficial for normal morphology, concentric remodeling and concentric hypertrophy, while beta1-selective blockers may be beneficial for eccentric hypertrophy in patients with EH.

Adult↗

PubMed2005

Modulation of cardiovascular remodeling with statins: fact or fiction?

The concept of cardiac remodeling implies a complex mixture of myocardial ischemia, and increased wall stress that results in molecular, cellular and interstitial changes in the heart. Clinically, cardiac remodeling is manifested as a change in size, shape and function of the heart. Morphologically the key feature of remodeling is myocyte hypertrophy, myocyte loss from necrosis or apoptosis, as well as interstitial cell growth especially fibroblast proliferation leading to myocardial fibrosis. Cardiac remodeling is influenced by hemodynamic load, neurohumoral activation, and other factors that can further affect the remodeling process. Despite advances in the management of heart failure, morbidity and mortality still present major health care issues in these patients. Statins (HMG Coenzyme A reductase inhibitors) play a key role in the management of ischemic heart disease. Recent studies indicate that statins may modulate cardiac remodeling by affecting signals that cause fibroblast growth, and myocyte hypertrophy and loss. In this paper we review the mechanisms of cardiac remodeling and the mechanisms of potential beneficial effects of statins on cardiac remodeling.

Animals↗

PubMed2026

Early Fibrotic Remodeling Remains Responsive to Autologous Fat Grafting: Histological Findings in a Rat Model.

BACKGROUND/AIM: Fibrosis-associated soft tissue remodeling involves progressive alterations in extracellular matrix composition, vascular architecture and tissue biomechanics. Early fibrotic lesions may remain biologically responsive before irreversible sclerosis develops. This study evaluated the histological evolution of bleomycin-induced soft tissue remodeling and the effects of autologous fat grafting in a rat model. MATERIALS AND METHODS: Twenty female Wistar rats received subcutaneous bleomycin (1 mg/kg/day for three consecutive days) to induce localized soft tissue remodeling. Autologous fat grafting was performed 17 days later. Clinical assessment was conducted at baseline, Day 17 and Day 31 using a standardized semi-quantitative score evaluating erythema, edema, skin elasticity, cutaneous mobility and ulceration or necrosis. Histological analysis was performed at predefined timepoints. RESULTS: Bleomycin induced reproducible early fibrotic remodeling characterized by collagen deposition, stromal hypercellularity, vascular remodeling and architectural distortion. The mean composite clinical score increased from 0 at baseline to 9.10±1.75 on Day 17 and decreased to 7.75±1.35 after fat grafting on Day 31 (p=0.00024). Histological examination demonstrated persistent fibrotic septa, fibroblast proliferation, vascular reorganization and partial integration of grafted adipose tissue, indicating ongoing tissue remodeling. CONCLUSION: Bleomycin-induced remodeling produced reproducible early fibrotic changes in dermal and subcutaneous tissues. Autologous fat grafting was associated with significant clinical improvement and histological evidence of continued tissue reorganization. This model supports investigation of regenerative therapies targeting early fibrosis-associated soft tissue remodeling.

Animals↗

PubMed2001

[Cardioprotective mechanism of ischemic preconditioning is impaired by postinfarct ventricular remodeling through angiotensin II type 1 receptor activation].

BACKGROUND: Activation of protein kinase C-linked receptors and subsequent opening of the mitochondrial adenosine triphosphate-sensitive K+ (mitoKatp) channel is crucial in preconditioning. This study examined whether post-infarct ventricular remodeling interferes with the preconditioning mechanism. METHODS AND RESULTS: Two weeks before isolation of hearts, rabbits underwent a sham operation or coronary ligation (COL) to induce remodeling. Isolated buffer perfused hearts were subjected to 30-min global ischemia/2-hr reperfusion, and infarct size was expressed as a percentage of the left ventricle (%I/LV), from which the scarred infarct by COL was excluded. Although %I/LV was similar in sham-operated and remodeled hearts (52.9 +/- 6.5% vs 45.8 +/- 5.2%), preconditioning with 2 episodes of 5-min ischemia protected sham-operated but not remodeled hearts (%I/LV = 18.1 +/- 2.5% vs 54.8 + 2.9%, p < 0.05). Infusion of valsartan (10 mg/kg/day; Val), an angiotensin II type 1 receptor blocker, for 2 weeks after COL prevented the ventricular remodeling and preserved the response to preconditioning (%I/LV = 27.4 +/- 3.8%), though Val alone did not change %I/LV. Diazoxide, a mitoKatp channel opener, protected both sham-operated and remodeled hearts (%I/LV = 14.1 +/- 3.1% and 8.3 +/- 3.6%). CONCLUSIONS: The myocardium remodeled after infarction is refractory to preconditioning, which is probably due to interruption of cellular signaling by preconditioning upstream of mitoKatp channels. An angiotensin II type 1 receptor blocker is beneficial not only for suppression of ventricular remodeling but also for preservation of the preconditioning mechanism.

Angiotensin Receptor Antagonists↗

PubMed2003

Stereo visualization of 3D trabecular bone structures produced by bone remodelling simulation.

Adult human bone is constantly being renewed by a process known as remodelling. For cancellous bone this renewal process occurs at the interface between bone and marrow where bone is depleted by osteoclasts and rebuilt by osteoblasts. This remodelling process allows bone to repair itself. Software simulators for bone remodelling provide insight into the bone remodelling process; they allow investigation into bone form and structural properties, and they also allow the emulation of bone diseases and possible treatments for these diseases over long periods of time. BONESIM is a software that simulates bone remodelling in terms of Basic Multi-cellular Units (BMUs). 3D visualization of trabecular bone and its attributes is an essential tool in understanding this remodelling process for cancellous bone. It enables the bone researcher to quickly understand the dynamic behaviour of remodelling, the resulting geometry of the bone structure and it allows alternative remodelling scenarios to be compared. This paper presents the volume visualization technique that has been developed to provide this visualization tool.

Adult↗

PubMed1999

Sustained elevation of plasma brain natriuretic peptide levels associated with progressive ventricular remodelling after acute myocardial infarction.

Previous studies have shown that levels of plasma brain natriuretic peptide (BNP) increase in an early phase of acute myocardial infarction. However, the relations between plasma BNP levels and left ventricular remodelling, which occurs long after acute myocardial infarction, are not fully understood. Venous plasma BNP levels were measured 2, 7, 14, 30, 90 and 180 days after the onset of acute myocardial infarction in 21 patients. Left ventricular end-diastolic volume index (EDVI, ml/m2) in acute (5 days) and chronic (6 months) phases were assessed by electron-beam computed tomography using Simpson's method. The remodelling group (n=9) was defined by an increase in EDVI >/=5 ml/m2 relative to the baseline value. Plasma BNP levels on days 2, 7, 14, 30 and 90 were significantly higher in the remodelling group than in the non-remodelling group (n=12, P<0.05). Sustained elevation of plasma BNP levels was noted from day 2 (61+/-12 pmol/l) to day 90 (55+/-12 pmol/l) and significantly decreased on day 180 (24+/-3 pmol/l) in the remodelling group. In contrast, plasma BNP levels significantly decreased from day 2 (25+/-4 pmol/l) to day 90 (9+/-1 pmol/l) and reached a steady level thereafter in the non-remodelling group. Plasma BNP levels on day 7 correlated positively with an increase in EDVI (r=0.70, P<0.001) from the acute to chronic phase. More importantly, the sustained elevation of plasma BNP (percentage decrease smaller than 25%) from day 30 to day 90 identified patients in the remodelling group with a sensitivity of 100% and a specificity of 83%. In conclusion, not only the high levels of plasma BNP in an acute phase, but also the sustained elevation of plasma BNP in a chronic phase, may be associated with progressive ventricular remodelling occurring long after acute myocardial infarction.

Adult↗

PubMed2006

Chromatin remodeling in DNA replication.

Chromatin remodeling complexes have evolved to solve a very basic problem for eukaryotic cells accommodation of the genome to fit the dimensions of the nucleus without loss of access to the DNA molecule. In the nucleus, DNA is wrapped around histones to form nucleosomes and other higher order compact chromatin structures. Chromatin remodeling complexes enable highly regulated access to DNA sequences in the context of chromatin, and it is well known that these complexes are involved in regulation of transcription. However, gene expression is not the only process that occurs in the nucleus. DNA has to be replicated, recombined, and repaired. In this regard, it is notable that the recent discoveries have linked ATP-dependent remodeling complexes to DNA damage repair. These results have raised challenging questions about the possible versatility of chromatin remodeling complexes in other nuclear activities, particularly in DNA replication, since a number of recent studies have suggested a connection between this essential cellular process and chromatin remodeling. However, the chromatin remodeling events regulating DNA replication have not been extensively investigated. The aim of this prospect is to summarize recent studies that implicate chromatin remodeling in DNA replication and to address potential roles of chromatin remodeling at various stages of eukaryotic DNA replication.

Adenosine Triphosphate↗

PubMed2001

Coronary artery distensibility and compensatory vessel enlargement--a novel parameter influencing vascular remodeling?

Vascular remodeling implies the concept of compensatory vessel enlargement to preserve luminal dimensions during atheromatous plaque development. However, negative remodeling, i.e. vessel shrinkage in response to plaque accumulation has also been described. So far, the factors influencing positive or negative remodeling are uncertain. We hypothesized that vascular distensibility, a measure of vessel compliance, is related to compensatory enlargement. In 58 patients undergoing intravascular ultrasound interrogation of a de novo lesion prior to coronary intervention, the cross-sectional vessel area (VA), lumen area (LA) and plaque area (PA = VA minus LA) were measured at end diastole and end systole at the lesion site and at the proximal and distal reference segments. Positive remodeling was defined to be present when the VA at the lesion was > 1.05 times larger than that at the proximal reference (group A), negative remodeling when the VA at the lesion was < 0.95 of the reference site (group C) and in-between was considered to be intermediate (group B). Vessel compliance was measured by calculating vascular distensibility. Results showed a similar LA at the lesion site in all groups (4.18+/-2.18 vs. 4.36+/-1.19 vs. 3.74+/-1.81 mm2, NS) while VA and PA were significantly larger in group A (17.19+/-5.08 vs. 14.22+/-3.66 and 12.45+/-4.82 mm2, p = 0.005 and 13+/-4.55 vs. 9.95+/-3.58 and 8.7+/-3.83, p = 0.003, respectively). Vascular distensibility at the proximal reference segment was significantly greater in group A (3.55+/-2.67 vs. 1.25+/-1.03 and 0.85+/-0.73 mmHg(-1), p < 0.001) with a positive correlation between remodeling and distensibility (R = 0.52, p < 0.001). In a multiple regression model including clinical and lesional factors, distensibility was the only predictor of remodeling. In conclusion, these results suggest that compensatory vessel enlargement occurs to a greater degree in patients with increased coronary artery distensibility, which appears to be a predictor for positive remodeling.

Adaptation, Physiological↗

PubMed2004

Prevention and Reversal of LV Remodeling with Neurohormonal Inhibitors.

Left ventricular (LV) remodeling refers to alterations in ventricular mass, chamber size, and shape that result from myocardial injury, pressure, or volume overload. Numerous studies have demonstrated that LV remodeling correlates with the incidence of heart failure and death, supporting a causative role for remodeling in heart failure progression. Heart failure trials have shown that neurohormonal antagonists, including angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic receptor blockers (beta blockers), reduce remodeling in parallel with improved clinical outcomes. Existing data favor using angiotensin II type 1 (AT1) receptor antagonists (or "ARBs"), although their anti-remodeling effects are less well established. Recently, mineralocorticoid receptor antagonists have gained substantial interest based on favorable clinical trial results, although data regarding their effects on remodeling are limited. Thus, an optimal medical regimen to prevent or limit LV remodeling in patients with LV dysfunction should include both an ACE inhibitor and beta-adrenergic receptor antagonist, irrespective of the degree of LV dysfunction and symptom status. For patients intolerant to ACE inhibitors, an AT1 receptor antagonist should be substituted. An aldosterone antagonist should be administered to patients with severe, New York Heart Association class III to IV heart failure who have normal or only mildly impaired renal function, or to those patients with depressed LV function following an acute myocardial infarction. Through the aggressive pharmacologic inhibition of both the renin-angiotensin-aldosterone and sympathetic nervous systems, progressive LV remodeling can be prevented or hindered, thereby favorably altering the natural history of the heart failure syndrome.

Journal Article↗

PubMed2004

Spectrum of remodeling behavior observed with serial long-term (>/=12 months) follow-up intravascular ultrasound studies in left main coronary arteries.

Most intravascular ultrasound (IVUS) studies of arterial remodeling in native coronary arteries reported a remodeling index obtained at a single time point. We analyzed serial IVUS examinations, including the vessel cross-sectional area changes (remodeling behavior), of 60 hemodynamically nonstenotic left main lesions (baseline vs 18.4 +/- 9.4 months follow-up). Lumen reduction resulted from vessel reduction (sometimes despite plaque + media decrease), plaque + media increase (with or without vessel increase), or both. The percent annual changes in lumen area correlated strongly with changes in vessel (r = 0.84), but not with changes in plaque + media area. Plaques were classified as group A lesions, reflecting positive remodeling behavior (vessel changes >0), or group B lesions, reflecting negative (or intermediate) remodeling behavior (vessel changes <==0). Both groups did not differ significantly in demographics, laboratory data, and medications. Group A lesions (n = 40) more often showed plaque + media increase than group B lesions (32 of 40 [80%] vs 9 of 20 [45%]; p = 0.02). Group A lesions had, on average, mild annual lumen increase despite mild plaque + media increase, i.e, overcompensation of remodeling for plaque + media increase (vessel increase greater than plaque + media area increase, 19 of 40 [47%]). Conversely, group B lesions (n = 20) showed a significant lumen area reduction (-2.8 +/- 2.6 mm(2)/year) as a result of a decrease in vessel area only. Thus, serial long-term reduction of lumen size may result from vessel shrinkage (sometimes despite plaque decrease), plaque increase (with or without vessel increase), or both; overall, only the remodeling behavior has a significant relation to lumen changes. More than 30% of lesions show a negative remodeling behavior, which shows no relation to patient characteristics or initial plaque burden.

Aged↗