Intimal Thickening (intimal + thickening)

Distribution by Scientific Domains


Selected Abstracts


EARLY ACTIVATION OF INTERNAL MEDIAL SMOOTH MUSCLE CELLS IN THE RABBIT AORTA AFTER MECHANICAL INJURY: RELATIONSHIP WITH INTIMAL THICKENING AND PHARMACOLOGICAL APPLICATIONS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2006
Huguette Louis
SUMMARY 1Smooth muscle cells (SMC) participate in both inflammatory and dedifferentiation processes during atherosclerosis, as well as during mechanical injury following angioplasty. In the latter, we studied medial SMC differentiation and inflammation processes implicated early after de-endothelialization in relation to mechanical stresses. We hypothesized that activation of a subpopulation of SMC within the media plays a crucial role in the early phase of neointimal formation. 2For this purpose, we used a rabbit model of balloon injury to study activation and differentiation of medial SMC in the early time after denudation and just before neointima thickening. Inflammation was evaluated by the expression of vascular cell adhesion molecule (VCAM)-1, integrin a4b1 and nuclear factor (NF)-kB. Myosin isoforms and 2P1A2 antigen, a membrane protein expressed by rabbit dedifferentiated SMC, were used as markers of differentiation. 3On day 2 after de-endothelialization, VCAM-1, a4b1 and NF-kB were coexpressed by a well-defined subpopulation of SMC of the internal part of the media, in the vicinity of the blood stream. At the same time, the majority of SMC throughout the media expressed non-muscle myosin heavy chain-B (nm-MHC-B) and 2P1A2 antigen. On day 7, when intimal thickening appeared, SMC of the media were no longer activated, whereas some intimal SMC expressed the activation markers. Thus, after de-endothelialization, early dedifferentiation occurs in most of the medial SMC, whereas activation concerned only a subpopulation of SMC located in the internal media. Using the T-type voltage-operated calcium channel blocker mibefradil (0.1,1 mmol/L) in SMC culture, we showed that this agent exhibited an antiproliferative effect in a dose-dependant manner only on undifferentiated cells. 4In conclusion, the results suggest that the activated SMC represent cells that are potentially able to migrate and participate in the intimal thickening process. Thus, the medial SMC inflammatory process, without any contribution of inflammatory cells, may represent a major mechanism underlying the development of intimal thickening following mechanical stress. In humans, inhibition of T-type calcium channels may be a tool to prevent the early proliferation step leading to neointimal formation. [source]


Coronary Flow Reserve by Transthoracic Echocardiography Predicts Epicardial Intimal Thickening in Cardiac Allograft Vasculopathy

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010
F. Tona
Cardiac allograft vasculopathy (CAV) is the leading cause of morbidity and mortality in heart transplantation (HT). We sought to investigate the role of coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) in CAV diagnosis. CAV was defined as maximal intimal thickness (MIT) assessed by intravascular ultrasound (IVUS) ,0.5 mm. CFR was assessed in the left anterior descending coronary artery in 22 HT recipients at 6 4 years post-HT. CAV was diagnosed in 10 patients (group A), 12 had normal coronaries (group B). The mean MIT was 0.7 0.1 mm (range 0.03,1.8). MIT was higher in group A (1.16 0.3 mm vs. 0.34 0.07 mm, p < 0.0001). CFR was 3.1 0.8 in all patients and lower in group A (2.5 0.6 vs. 3.7 0.3, p < 0.0001). CFR was inversely related with MIT (r =,0.774, p < 0.0001). A cut point of ,2.9, identified as optimal by receiver operating characteristics analysis was 100% specific and 80% sensitive (PPV = 100%, NPV = 89%, Accuracy = 91%). CFR assessment by CE-TTE is a novel noninvasive diagnostic tool in the detection of CAV defined as MIT ,0.5 mm. CFR by CE-TTE may reduce the need for routine IVUS in HT. [source]


Liposome-enhanced MRI of neointimal lesions in the ApoE-KO mouse

MAGNETIC RESONANCE IN MEDICINE, Issue 5 2006
Willem J.M. Mulder
Abstract Conventional high-resolution MRI is capable of detecting lipid-rich atherosclerotic plaques in both human atherosclerosis and animal models of atherosclerosis. In this study we induced neointimal lesions in ApoE-KO mice by placing a constrictive collar around the right carotid artery. The model was imaged with conventional multispectral MRI, and the thickened wall could not be distinguished from surrounding tissue. We then tested paramagnetic liposomes (mean size = 90 nm) for their ability to improve MRI visualization of induced thickening, using Gd-DTPA as a control. T1 -weighted (T1 -w), black-blood MRI of the neck area of the mice was performed before and 15 min, 45 min, and 24 hr after intravenous injection of either paramagnetic liposomes or Gd-DTPA. The collared vessel wall of mice that were injected with liposomes showed a pronounced signal enhancement of ,100% immediately after injection, which was sustained largely until 24 hr postinjection. In contrast, the vessel wall of all controls (left carotid artery and animals injected with Gd-DTPA) did not show significant contrast enhancement at those time points. This study demonstrates that intimal thickening in ApoE-KO mice can be effectively detected by contrast-enhanced (CE)-MRI upon injection of paramagnetic liposomes. Magn Reson Med, 2006. 2006 Wiley-Liss, Inc. [source]


An Integrated View of Molecular Changes, Histopathology and Outcomes in Kidney Transplants

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010
P. F. Halloran
Data-driven approaches to deteriorating kidney transplants, incorporating histologic, molecular and HLA antibody findings, have created a new understanding of transplant pathology and why transplants fail. Transplant dysfunction is best understood in terms of three elements: diseases, the active injury,repair response and the cumulative burden of injury. Progression to failure is mainly attributable to antibody-mediated rejection, nonadherence and glomerular disease. Antibody-mediated rejection usually develops late due to de novo HLA antibodies, particularly anti-class II, and is often C4d negative. Pure treated T cell-mediated rejection does not predispose to graft loss because it responds well, even with endothelialitis, but it may indicate nonadherence. The cumulative burden of injury results in atrophy-fibrosis (nephron loss), arterial fibrous intimal thickening and arteriolar hyalinosis, but these are not progressive without ongoing disease/injury, and do not explain progression. Calcineurin inhibitor toxicity has been overestimated because burden-of-injury lesions invite this default diagnosis when diseases such as antibody-mediated rejection are missed. Disease/injury triggers a stereotyped active injury,repair response, including de-differentiation, cell cycling and apoptosis. The active injury,repair response is the strongest correlate of organ function and future progression to failure, but should always prompt a search for the initiating injury or disease. [source]


Cluster Analysis of Lesions in Nonselected Kidney Transplant Biopsies: Microcirculation Changes, Tubulointerstitial Inflammation and Scarring

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010
B. Sis
Banff classification empirically established scoring of histologic lesions, but the relationships of lesions to each other and to underlying biologic processes remain unclear. We hypothesized that class discovery tools would reveal new relationships between individual lesions, and relate lesions to C4d staining, anti-HLA donor-specific antibody (DSA) and time posttransplant. We studied 234 nonselected renal allograft biopsies for clinical indications from 173 patients. Silhouette plotting and principal component analysis revealed three groups of lesions: microcirculation changes, including inflammation (glomerulitis, capillaritis) and deterioration (double contours, mesangial expansion); scarring/hyalinosis; and tubulointerstitial inflammation. DSA and C4d grouped with microcirculation inflammation, whereas time posttransplant grouped with scarring/hyalinosis lesions. Intimal arteritis clustered with DSA, C4d and microcirculation inflammation, but also showed correlations with tubulitis. Fibrous intimal thickening in arteries clustered with scarring/hyalinosis. Capillary basement membrane multilayering showed intermediary relationships between microcirculation deterioration and time-dependent scarring. Correlation analysis and hierarchical clustering confirmed the lesion relationships. Thus, we propose that the pathologic lesions in biopsies are not independent but are members of groups that represent distinct pathogenic forces: microcirculation changes, reflecting the stress of DSA; scarring, hyalinosis and arterial fibrosis, reflecting the cumulative burden of injury over time; and tubulointerstitial inflammation. Interpretation of lesions should reflect these associations. [source]


Call for Revolution: A New Approach to Describing Allograft Deterioration

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2002
Philip F. Halloran
I propose a set of definable entities in the renal transplant course, eliminating the need for the term ,chronic rejection'. The status of a renal transplant can be defined by the presence and extent of rejection (T-cell-mediated or antibody-mediated); allograft nephropathy (parenchymal atrophy, fibrosis, and fibrous intimal thickening in arteries); transplant glomerulopathy; specific diseases; and factors which could accelerate progression. The level of function and the slope of the loss of function should be separately determined. This approach can be applied both in research and in clinical practice, and can be adapted to other organ transplants. [source]


Effects of the combination of rapamycin with tacrolimus or cyclosporin on experimental intimal hyperplasia

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 11 2002
Dr J. R. Waller
Background: Allograft vasculopathy remains the leading cause of late allograft failure following transplantation and can be inhibited by the antiproliferative drug rapamycin. This study assessed the efficacy of combining rapamycin therapy with calcineurin inhibition. Methods: Male Sprague,Dawley rats received rapamycin 005 mg/kg daily and either tacrolimus 01 mg/kg or cyclosporin 5 mg/kg daily, and findings were compared with those in an untreated control group. Animals underwent left common carotid artery balloon angioplasty; the artery was explanted after 2 weeks. Morphometric analysis was performed on transverse sections and the intima: media ratio was calculated. Profibrotic gene expression was measured with competitive reverse transcriptase,polymerase chain reaction at 14 and 28 days. Proliferation was determined with proliferating cell nuclear antigen at 14 and 28 days. Extracellular matrix deposition was quantified with Sirius red. Results: The combination of rapamycin and tacrolimus was associated with the greatest reduction in intimal thickening. Furthermore, treatment with rapamycin and tacrolimus significantly attenuated extracellular matrix deposition compared with rapamycin and cyclosporin (P < 002). Conclusion: The effects of rapamycin in combination with tacrolimus were better than those observed with rapamycin and cyclosporin. 2002 British Journal of Surgery Society Ltd [source]


Prospective analysis of carotid artery flow in breast cancer patients treated with supraclavicular irradiation 8 or more years previously,

CANCER, Issue 2 2008
No increase in ipsilateral carotid stenosis after radiation noted
Abstract BACKGROUND. To the authors' knowledge, the effects of supraclavicular fossa radiation on the carotid artery are not well described. In the current study, the authors performed a prospective study to examine the long-term risk of carotid artery stenosis after supraclavicular irradiation for breast cancer. METHODS. A total of 46 breast cancer patients who were treated with adjuvant radiation to the supraclavicular fossa with >8 years of follow-up underwent bilateral Doppler imaging of the carotid artery. Two independent cardiologists interpreted each ultrasound study with no knowledge of which side was treated. RESULTS. The median follow-up from the date of diagnosis was 14.6 years and the mean patient age at the time of ultrasound was 55 years. The median prescribed dose to the supraclavicular fossa was 50 grays. Four patients were found to have clinically relevant, asymptomatic carotid stenosis, for which a cardiology referral was necessary. Only 1 of these 4 patients had stenosis involving the irradiated carotid artery only; 1 patient had bilateral stenosis and 2 patients had only contralateral stenosis. There was no difference noted with regard to isolated ipsilateral versus contralateral medial intimal thickening of the carotid artery (5 patients vs 6 patients, respectively). Furthermore, there were no differences noted with regard to ipsilateral versus contralateral peak systolic flow in the internal (83.5 vs 85.6 cm/seconds; P = .522 by the Student t test and P = .871 by the signed rank test) or common (74.4 vs 77.0 cm/seconds; P = .462 by the Student t test and P = .246 by the signed rank test) carotid artery. CONCLUSIONS. In this prospective study of breast cancer patients with long follow-up, there was no evidence of late, clinically relevant stenosis, increased intimal thickening, or increased peak systolic carotid artery flow secondary to supraclavicular irradiation. Cancer 2008. 2007 American Cancer Society. [source]


Hypereosinophilic syndrome with various skin lesions and juvenile temporal arteritis

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 5 2009
K. Ito
Summary Hypereosinophilic syndrome (HES) is a multisystem disease with a high mortality rate. It is characterized by peripheral blood eosinophilia and eosinophilic infiltration of the skin and many other organs. The commonest cutaneous features include erythematous pruritic maculopapules and nodules, angio-oedema or urticarial plaques. However, some case reports have indicated that eosinophilic cellulitis, cutaneous necrotizing eosinophilic vasculitis, Raynaud's phenomenon and digital gangrene may also occur as cutaneous features of HES. Juvenile temporal arteritis (JTA) of unknown cause is characterized by an asymptomatic nodule in the temporal artery area in young adults. Histologically, the lesion is characterized by a significant intimal thickening with moderate eosinophilic infiltrates, constriction or occlusion of the vascular lumen and absence of giant cells. We report a patient with HES presenting with eosinophilic cellulitis, Raynaud's phenomenon, digital gangrene and JTA. JTA may also be one of the features of HES. [source]


EARLY ACTIVATION OF INTERNAL MEDIAL SMOOTH MUSCLE CELLS IN THE RABBIT AORTA AFTER MECHANICAL INJURY: RELATIONSHIP WITH INTIMAL THICKENING AND PHARMACOLOGICAL APPLICATIONS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2006
Huguette Louis
SUMMARY 1Smooth muscle cells (SMC) participate in both inflammatory and dedifferentiation processes during atherosclerosis, as well as during mechanical injury following angioplasty. In the latter, we studied medial SMC differentiation and inflammation processes implicated early after de-endothelialization in relation to mechanical stresses. We hypothesized that activation of a subpopulation of SMC within the media plays a crucial role in the early phase of neointimal formation. 2For this purpose, we used a rabbit model of balloon injury to study activation and differentiation of medial SMC in the early time after denudation and just before neointima thickening. Inflammation was evaluated by the expression of vascular cell adhesion molecule (VCAM)-1, integrin a4b1 and nuclear factor (NF)-kB. Myosin isoforms and 2P1A2 antigen, a membrane protein expressed by rabbit dedifferentiated SMC, were used as markers of differentiation. 3On day 2 after de-endothelialization, VCAM-1, a4b1 and NF-kB were coexpressed by a well-defined subpopulation of SMC of the internal part of the media, in the vicinity of the blood stream. At the same time, the majority of SMC throughout the media expressed non-muscle myosin heavy chain-B (nm-MHC-B) and 2P1A2 antigen. On day 7, when intimal thickening appeared, SMC of the media were no longer activated, whereas some intimal SMC expressed the activation markers. Thus, after de-endothelialization, early dedifferentiation occurs in most of the medial SMC, whereas activation concerned only a subpopulation of SMC located in the internal media. Using the T-type voltage-operated calcium channel blocker mibefradil (0.1,1 mmol/L) in SMC culture, we showed that this agent exhibited an antiproliferative effect in a dose-dependant manner only on undifferentiated cells. 4In conclusion, the results suggest that the activated SMC represent cells that are potentially able to migrate and participate in the intimal thickening process. Thus, the medial SMC inflammatory process, without any contribution of inflammatory cells, may represent a major mechanism underlying the development of intimal thickening following mechanical stress. In humans, inhibition of T-type calcium channels may be a tool to prevent the early proliferation step leading to neointimal formation. [source]