Intimal Hyperplasia (intimal + hyperplasia)

Distribution by Scientific Domains


Selected Abstracts


Heparin Coating of Small-Caliber Decellularized Xenografts Reduces Macrophage Infiltration and Intimal Hyperplasia

ARTIFICIAL ORGANS, Issue 6 2009
Wei-Wei Cai
Abstract Small-caliber decellularized xenografts with surface heparin coating are known to reduce in vivo thrombogenicity. This study was performed to examine whether heparin coating on the small-caliber decellularized xenografts would reduce macrophage infiltration and intimal hyperplasia. In a rabbit model of bilateral carotid implantation, each of the animals (n = 18) received a heparin-coated decellularized xenograft from a canine carotid artery on one side and a nonheparin-coated one on the other side. These experiments were terminated respectively at 1 week (n = 6), 3 weeks (n = 6), and 12 weeks (n = 6). Results showed that, compared with the nonheparin-coated grafts, the heparin-coated grafts had significantly less macrophage infiltration 1 week after implantation, identified by the mouse antirabbit macrophage antibody (RAM11)-positive cells on the vascular wall, covering all the proximal, middle, and distal parts of the grafts (P < 0.01). Moreover, the heparin-coated grafts also showed less deposition of proliferation cell nuclear antigen (PCNA)-positive cells on the vascular wall, indicating less cell proliferation, which was significant not only at 1 week (P < 0.01) but also at 12 weeks (P < 0.01). Intimal hyperplasia, measured by the intimal : media (I : M) ratio, was found similar in both groups at 1 and 3 weeks. However, the I : M ratio was significantly lower in the heparin-coated group than in the nonheparin-coated group at 12 weeks, especially in the proximal anastomosis area (0.76 0.12 vs. 0.345 0.06, P < 0.01). Heparin coating of small-caliber decellularized xenografts is associated with an early reduction of macrophage infiltration and intimal hyperplasia in a rabbit model of bilateral carotid artery implantation for 12 weeks. Thus, heparin coating appears to deliver not only the antithrombogeneity but also the antiproliferative property for small-caliber decellularized xenografts. [source]


Intima-media thickness of radial artery is associated with early access failure in hemodialysis patients

HEMODIALYSIS INTERNATIONAL, Issue 1 2005
Y.O. Kim
Objective:,We have reported that intimal hyperplasia, which is the pathologic change of the radial artery, is associated with early failure of arteriovenous fistula (AVF) in hemodialysis (HD) patients (Am J Kidney Dis, 41:422,428, 2003). Intima-media thickness (IMT), which represents the whole thickness of arterial wall, can be easily measured by ultrasonography, unlike intima thickness. This study was performed to investigate the impact of IMT of radial artery on early failure of AVF in HD patients. Methods:,Ninety HD patients undergoing radiocephalic AVF operation were included in this study. The AVF was constructed in an end vein,to,side artery fashion at the wrist by one vascular surgeon. During the operation, 10-mm long partial arterial walls were removed with elliptical form for microscopic analysis. Specimens were stained with trichrome and examined by a pathologist blinded to the clinical data. AVF patency was prospectively followed up for 1 year after the operation. Results:,Mean age of the patients was 56 13 years and the number of females was 44 (48.9%). Mean IMT was 430 132 ,m (133,760 ,m). Of the total 90 patients, 31 patients (34.4%) had AVF failure within 1 year after the operation. Mean IMT was higher in the failed group (n = 31) than in patent group (n = 59)(486 130 ,m vs. 330 178 ,m, p = 0.004). Using a threshold of 500 ,m of IMT, AVF patency rate was compared between these two groups using Kaplan-Meier method with log rank test. The AVF patency rate within 1 year after the operation was higher in patients with IMT , 500 ,m (n = 26) than in patients with IMT < 500 ,m (n = 64)(p < 0.001). The patients with IMT , 500 ,m were older and had higher incidence of diabetes mellitus, compared to the patients with IMT < 500 ,m. There was no difference in sex, smoking, hypertension, total cholesterol and albumin levels between the two groups. Conclusion:,Our data suggest that increased intima-media thickness of radial artery is associated with early failure of radiocephalic arteriovenous fistula in hemodialysis patients. [source]


Quantitative determination of the diagnostic accuracy of the synovitis score and its components

HISTOPATHOLOGY, Issue 3 2010
Elisabeth Slansky
Slansky E, Li J, Hupl T, Morawietz L, Krenn V & Pessler F (2010) Histopathology,57, 436,443 Quantitative determination of the diagnostic accuracy of the synovitis score and its components Aims:, To assess the diagnostic accuracy of a three-component synovitis score and to determine the relative contribution of each of its components to its overall discriminatory power. Methods and results:, The synovitis score was determined in 666 synovial specimens: normal synovium, n = 33; post-traumatic arthropathy (PtA), n = 29; osteoarthritis (OA), n = 221; psoriatic arthritis (PsA), n = 42; and rheumatoid arthritis (RA), n = 341. The discriminatory abilities of the score and its components were quantified with binary and multicategory receiver operating characteristic (ROC) analysis. The score differentiated all arthropathies accurately from normal tissue (area under the ROC curve, AUC: 0.87,0.98) and RA from OA or PtA (AUC: 0.85 for both), but could not distinguish well within pairs of inflammatory or degenerative arthropathies. AUCs of the intimal hyperplasia and stromal cellularity components correlated with the AUCs of the complete score markedly more strongly (r = 0.94 and 0.91, respectively) than the inflammatory infiltration component (r = 0.60). Multicategory ROC analysis ranked the score several-fold higher than any of its components, and the components in the order stromal cellularity>intimal hyperplasia>infiltration. Conclusion:, Combining three distinct histological parameters into a three-component score produces greatly increased overall diagnostic power. The discriminatory ability of the score stems more from measuring proliferative than infiltrative aspects of synovitis. [source]


Comparison study of Doppler ultrasound surveillance of expanded polytetrafluoroethylene-covered stent versus bare stent in transjugular intrahepatic portosystemic shunt

JOURNAL OF CLINICAL ULTRASOUND, Issue 7 2010
Qian Huang MD
Abstract Objective. This prospectively randomized controlled study aimed to assess with Doppler ultrasound (US) the shunt function of expanded polytetrafluoroethylene (ePTFE)-covered transjugular intrahepatic portosystemic shunt (TIPS) stent versus bare stent and to evaluate the usefulness of routine TIPS follow-up of ePTFE-covered stents. Methods. Sixty consecutive patients were randomized for bare or covered transjugular TIPS stenting in our institution between April 2007 and April 2009. Data of follow-up Doppler US, angiography, and portosystemic pressure gradient measurements were collected and analyzed. Results. The follow-up period was 8.34 4.42 months in the bare-stent group and 6.16 3.89 months in the covered-stent group. Baseline clinical characteristics were similar in both groups. Two hundred three US studies were performed in 60 patients, with a mean of 3.4 per patient, and demonstrated abnormalities in 28 patients (21 bare stents, 7 ePTFE-covered stents), 19 of them (13 in bare-stent group, 6 in covered-stent group) showing no clinical evidence of recurrence. Ten of 13 patients in the bare-stent group underwent balloon angioplasty or additional stent placement, whereas only one of six patients in the covered-stent group needed reintervention for intimal hyperplasia. The average peak velocity in the midshunt of ePTFE-covered stent was 139 26 cm/s after TIPS creation and 125 20 cm/s during follow-up, which was significantly higher than the bare-stent group (p < 0.05). The main portal vein and hepatic artery showed higher flow velocities in the ePTFE-covered stent group than in the bare-stent group. ePTFE-covered stents maintained lower portosystemic pressure gradient than bare stents (9.5 2.9 versus 13.2 1.5 mmHg, p < 0.05). Conclusions. ePTFE-covered stents resulted in higher patency rates and better hemodynamics than bare stents. Routine US surveillance may not be necessary in patients with ePTFE-covered TIPS stent. 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:353-360, 2010 [source]


Efficacy and Safety of Absorbable Metallic Stents with Adjunct Intracoronary Beta Radiation in Porcine Coronary Arteries

JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 5 2007
F.A.C.C., RON WAKSMAN M.D.
Background: Absorbable metallic stents (AMS) utilizing Mg alloy carry advantages over permanent metallic stents because of their potential to eliminate stent thrombosis, chronic inflammation, or artifacts with noninvasive imaging. These stents, however, are associated with a modest degree of late recoil and intimal hyperplasia. The aim of the study was to test whether adjunct vascular brachytherapy (VBT) compared to AMS alone can overcome these limitations. Methods: Juvenile domestic pig coronary arteries underwent implantation of either AMS (n = 11) with prior adjunct VBT utilizing Sr/Y-90 , source seeds, with a dose of 24 Gy at 2 mm from the source, or AMS alone (n = 11). At 28 days following intravascular ultrasound, vessels were harvested and analyzed by histomorphometry. Results: Intravascular ultrasound analysis indicated that at follow-up, though statistically not significant, lumen and stent areas in the segments deployed with AMS following radiation were larger than those deployed with AMS alone (3.94 1.38 and 3.53 1.75 vs. 2.99 1.05 and 3.58 1.48). Extrastent plaque and intrastent plaque areas in the same segments were smaller (2.76 0.82 and 0.24 0.47 vs. 3.25 1.94 and 0.58 0.81). Morphometric data indicate that vessels in the VBT + AMS group showed characteristics of delayed healing and re-endothelialization. Neointimal area was significantly lower in the VBT + AMS group (0.49 0.34) compared to AMS (1.3 0.62, P = 0.001). Lumen area of the VBT + AMS was larger when compared with AMS alone (2.49 0.82 vs. 1.75 0.51, P = 0.02). Conclusion: VBT as an adjunct to AMS further reduces the intimal hyperplasia and improves the lumen area when compared to AMS alone but does not have any impact on late recoil. [source]


Postinjury vascular intimal hyperplasia in mice is completely inhibited by CD34+ bone marrow-derived progenitor cells expressing membrane-tethered anticoagulant fusion proteins

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2006
D. CHEN
Summary.,Background:,Coagulation proteins promote neointimal hyperplasia and vascular remodelling after vessel injury, but the precise mechanisms by which they act in vivo remain undetermined. Objectives:,This study, using an injury model in which the neointima is derived from bone marrow (BM)-derived cells, compared inhibition of tissue factor or thrombin on either BM-derived or existing vascular smooth muscle cells. Methods:,Two transgenic (Tg) mouse strains expressing membrane-tethered tissue factor pathway inhibitor (TFPI) or hirudin (Hir) fusion proteins driven by an , smooth muscle actin (SMA) promoter were generated (, -TFPI-Tg and , -Hir-Tg) and the phenotype after wire-induced endovascular injury was compared with that in wild-type (WT) controls. Results:,WT mice developed progressive neointimal expansion, whereas injury in either Tg was followed by repair back to a preinjured state. This was also seen when WT mice were reconstituted with BM from Tg mice but not when Tgs were reconstituted with WT BM, in which injury was followed by slowly progressive neointimal expansion. Injection of CD34+ cells from Tg mice into injured WT mice resulted in the accumulation of fusion protein-expressing cells from day 3 onwards and an absence of neointimal hyperplasia in those areas. Conclusions:,Neointimal development after wire-induced endovascular injury in mice was completely inhibited when BM-derived cells infiltrating the damaged artery expressed membrane tethered anticoagulant fusion proteins under an , -SMA promoter. These findings enhance our understanding of the pathological role that coagulation proteins play in vascular inflammation. [source]


The role of the fibrocyte in intimal hyperplasia

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2006
R. L. VARCOE
Summary.,Background: Experimental animal studies have shown that the intimal hyperplasia (IH) responsible for occlusion after successful revascularization procedures may be partially caused by a bone marrow-derived cell that migrates to the site of vascular injury. Concurrent studies have demonstrated an extensive role in wound healing for the circulating fibrocyte. Objectives: We aimed to trace the path of the circulating cell that contributes to IH and determine if it is the fibrocyte. Methods and results: We established an in vitro model whereby purified monocytes from six healthy human volunteers were cultured into fibrocytes. These cells were morphometrically similar to the vascular smooth muscle cell (VSMC) found in IH and expressed alpha-smooth muscle actin (, -SMA) as well as CD34, CD45 and Collagen I (Col I), markers indicative of the fibrocyte. In an in vivo ovine carotid artery synthetic patch graft model, carboxyfluorescein diacetate, succinimidyl ester (CFSE) labeled circulating leukocytes were observed throughout the graft as well as in the neointima in 18 sheep. These cells were shown to produce collagen and , -SMA at 1, 2 and 4 weeks. These cells then underwent immunohistochemical analysis and were found to express a set of markers unique to the fibrocyte (CD34, CD45, Vimentin and , -SMA) and also to double stain for CD34 and , -SMA. Conclusions: IH in an ovine carotid artery patch graft model is partially derived from a hematopoietic circulating progenitor cell that acquires mesenchymal features as it matures at the site of injury. [source]


Gangliosides in rat femoral injury: Early effect on intimal hyperplasia

MICROSURGERY, Issue 4 2001
Leonardo C. Castro
Previous studies demonstrated that some immunosupressive agents inhibit arterial intimal hyperplasia. Our previous studies demonstrated that gangliosides (Gang) have an immunosuppressive effect on as well as an anti-inflammatory role in the wound-healing process. Therefore, we decided to examine the effect of Gang on intimal hyperplasia. Twenty Wistar isogenic rats received a transverse division of the anterior wall of the femoral artery, followed by suturing using mononylon 10-0 under surgical microscopy and were then divided into two groups: Gang group, 3 mg/kg per day of Gang, and control group, vehicle, intramuscularly from surgery to death (1 and 3 weeks, respectively). Concentric intimal hyperplasia was observed in arteries stained by hematoxylin-eosin in control and Gang groups. However, the media layer did not demonstrate any major alterations. After 3 weeks, the Gang group showed more intimal hyperplasia than the control group. Therefore, because intimal hyperplasia worsened in the presence of Gang after 3 weeks, further studies will be necessary to clarify its role in intimal proliferation. 2001 Wiley-Liss, Inc. MICROSURGERY 21:170,172 2001 [source]


Vascular closure staples reduce intimal hyperplasia in prosthesis implantation

ANZ JOURNAL OF SURGERY, Issue 12 2002
Wayne J. Hawthorne
Background: Vascular surgery, like the various other surgical specialities, has seen an increasing demand toward faster and more minimally invasive procedures. One such need is to create a reliable vascular anastomosis that is faster, easier and less damaging to the tissue. The vascular closure staples (VCS*) device provides such characteristics but, to date, no studies have investigated its effectiveness in reducing intimal hyperplasia when used for vascular prosthesis implantation. The present study evaluated its effectiveness compared with suturing of a graft in vascular prosthesis implantation. Methods: Twelve female Merino sheep underwent gelatin sealed Dacron patch graft implantation into the left and right common carotid artery. Grafts were randomly allocated so that one carotid artery and graft was anastomosed using sutures and the other with VCS*. The two techniques were compared for operation time, clip/suture numbers and blood loss during the implantation procedure. After a 4-week period, the sheep were killed and the grafts were harvested for intimal hyperplasia (IH) assessment. Results: There was a significant reduction in the amount of IH seen in the VCS* group (mean SD: 0.278 0.079 mm2/mm) when compared with the sutured group (0.575 0.331 mm2/mm) (P < 0.05). There was also significant reduction in anastomosis time (mean SD: 14 4.4 min) and fewer points of contact (23 1.4) using the VCS* compared with suturing (22 3.2 min, P < 0.01; 27 3.3, P < 0.05, respectively). Conclusions: In this model, the VCS* shows several distinct advantages over suturing with significant time saving at operation and, most importantly, the reduction of IH seen at 1 month. [source]


Alcohol Pretreatment of Small-diameter Expanded Polytetrafluoroethylene Grafts: Quantitative Analysis of Graft Healing Characteristics in the Rat Abdominal Aorta Interposition Model

ARTIFICIAL ORGANS, Issue 7 2009
Erman Pektok
Abstract Long-term patency rates of small-diameter expanded polytetrafluoroethylene (ePTFE) vascular prostheses are unsatisfactory. Treatment of ePTFE grafts by alcohol before implantation was reported to increase hydrophilic properties, yielding better endothelialization and cellular in-growth, thus improving graft healing. The effect of alcohol pretreatment on ePTFE grafts and postoperative healing characteristics of wet ePTFE grafts were evaluated in this study. Ten sterile ePTFE grafts (2 mm ID, 30 thru-pore, 12 mm long) were implanted in the infrarenal aorta of male Sprague-Dawley rats (324,380 g). Five grafts were treated with ethanol 70% and soaked with saline solution before implantation (wet); five nontreated grafts served as control. All rats were sacrificed after digital subtraction angiography and sampling of the graft for histological investigation after 3 weeks. Histomorphometric analysis was performed for endothelial coverage, cellular in-growth, and intimal hyperplasia. All grafts were patent at the end of 3 weeks in both groups. Histological evaluation revealed significantly better endothelial coverage and prominent infiltration by fibroblasts and lymphocytes in the wet group. Endothelial coverage (31.03 10.61% vs. 13.03 9.46%, P = 0.03) and cellular infiltration of grafts (50.91 8.55% vs. 39.29 10.70%, P = 0.11) were higher in the wet group. Area of intimal hyperplasia per graft length was also higher in the wet group (5.32 4.75 m2/m vs. 2.69 3.41 m2/m, P = 0.36). Wetting of ePTFE grafts with ethanol 70% pretreatment before implantation might have a beneficial effect on long-term patency of small-diameter vascular grafts due to facilitated graft healing. [source]


Heparin Coating of Small-Caliber Decellularized Xenografts Reduces Macrophage Infiltration and Intimal Hyperplasia

ARTIFICIAL ORGANS, Issue 6 2009
Wei-Wei Cai
Abstract Small-caliber decellularized xenografts with surface heparin coating are known to reduce in vivo thrombogenicity. This study was performed to examine whether heparin coating on the small-caliber decellularized xenografts would reduce macrophage infiltration and intimal hyperplasia. In a rabbit model of bilateral carotid implantation, each of the animals (n = 18) received a heparin-coated decellularized xenograft from a canine carotid artery on one side and a nonheparin-coated one on the other side. These experiments were terminated respectively at 1 week (n = 6), 3 weeks (n = 6), and 12 weeks (n = 6). Results showed that, compared with the nonheparin-coated grafts, the heparin-coated grafts had significantly less macrophage infiltration 1 week after implantation, identified by the mouse antirabbit macrophage antibody (RAM11)-positive cells on the vascular wall, covering all the proximal, middle, and distal parts of the grafts (P < 0.01). Moreover, the heparin-coated grafts also showed less deposition of proliferation cell nuclear antigen (PCNA)-positive cells on the vascular wall, indicating less cell proliferation, which was significant not only at 1 week (P < 0.01) but also at 12 weeks (P < 0.01). Intimal hyperplasia, measured by the intimal : media (I : M) ratio, was found similar in both groups at 1 and 3 weeks. However, the I : M ratio was significantly lower in the heparin-coated group than in the nonheparin-coated group at 12 weeks, especially in the proximal anastomosis area (0.76 0.12 vs. 0.345 0.06, P < 0.01). Heparin coating of small-caliber decellularized xenografts is associated with an early reduction of macrophage infiltration and intimal hyperplasia in a rabbit model of bilateral carotid artery implantation for 12 weeks. Thus, heparin coating appears to deliver not only the antithrombogeneity but also the antiproliferative property for small-caliber decellularized xenografts. [source]


Computational Fluid Dynamics and Vascular Access

ARTIFICIAL ORGANS, Issue 7 2002
Ulf Krueger
Abstract: Anastomotic intimal hyperplasia caused by unphysiological hemodynamics is generally accepted as a reason for dialysis access graft occlusion. Optimizing the venous anastomosis can improve the patency rate of arteriovenous grafts. The purpose of this study was to examine, evaluate, and characterize the local hemodynamics and, in particular, the wall shear stresses in conventional venous end-to-side anastomosis and in patch form anastomosis (Venaflo) by three-dimensional computational fluid dynamics (CFD). We investigated the conventional form of end-to-side anastomosis and a new patch form by numerical simulation of blood flow. The numerical simulation was done with a finite volume-based algorithm. The anastomotic forms were constructed with usual size and fixed walls. Subdividing the flow domain into multiple control volumes solved the fundamental equations. The boundary conditions were identical for both forms. The velocity profile of the patch form is better than that for the conventional form. The region of high static pressure caused by flow stagnation is reduced on the vein floor. The anastomotic wall shear stress is decreased. The results of this study strongly support patch form use to reduce the incidence of intimal hyperplasia and venous anastomotic stenoses. [source]


Effects of local delivery of trapidil on neointima formation in a rabbit angioplasty model

BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2000
Kai Zacharowski
Smooth muscle cell (SMC) proliferation can result in luminal reduction of a vessel following balloon angioplasty. This study was designed (i) to determine if local administration of trapidil (triazolopyrimidine) into a vessel wall reduces neointima formation, and (ii) to explore the mechanism involved in the subsequent reduction in cell proliferation. Following balloon angioplasty in 40 anaesthetized New Zealand White rabbits, trapidil (50,200 mg) or its vehicle (saline) was injected into the dilated vessel wall of the right femoral artery. Experimental groups and time of investigation: (I) vehicle (2 weeks, n=3), (II) trapidil-100 mg (2 weeks, n=3), (III) vehicle (3 weeks, n=8), (IV) trapidil-50 mg (3 weeks, n=5); (V) trapidil-100 mg (3 weeks, n=9) or (V) trapidil-200 mg (3 weeks, n=7). After 2 weeks, there was a significant reduction of intimal hyperplasia (expressed as intima to media area ratio) in the trapidil group compared with vehicle (0.440.04 vs 0.930.04, *P<0.05) and also a significant reduction in cell proliferation (% ratio of BrdU-positive cells to total cell number: vehicle 142% vs trapidil 61%, *P<0.05). After 3 weeks, there was a dose-dependent reduction of intimal hyperplasia in the trapidil groups compared with vehicle (trapidil 50 mg 1.140.04; trapidil 100 mg 0.910.09*; trapidil 200 mg 0.770.09* vs vehicle 1.670.23, *P<0.05). Thus, the local administration of trapidil to the rabbit femoral artery reduces the neointima formation, which occurs 2 or 3 weeks after balloon angioplasty via a mechanism, which is dependent on inhibition of cell proliferation. British Journal of Pharmacology (2000) 129, 566,572; doi:10.1038/sj.bjp.0703098 [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]


Smooth muscle cell proliferation but not neointimal formation is dependent on alloantibody in a murine model of intimal hyperplasia

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2006
B. Soleimani
Summary Transplant coronary artery disease is the pre-eminent cause of late cardiac allograft failure. It is primarily characterized by a concentric intimal hyperplasia, which we designate transplant intimal hyperplasia (TIH). Although the pathogenesis of TIH is predominately immune driven, the specific role of alloantibodies in the disease process remains undefined. In this study we investigated the contribution of alloantibodies to the development of TIH in a murine model. Orthotopic, carotid artery transplantation was performed between B10A(2R) (H-2h2) donor mice and B-cell deficient ,MT,/, knockout or wild-type C57BL/6 (H-2b) recipients in the absence of immunosuppression. Grafts were harvested at 35 days and subjected to planimetry and immunohistochemistry. Alloantibodies were detectable in wild-type recipients within 7 days of transplantation and recipients developed marked TIH at 35 days. Allografts harvested from B-cell deficient recipient mice also developed TIH, which was comparable in severity with wild-type recipients. However, whereas allografts from wild-type recipients showed marked intimal smooth muscle cell (SMC) proliferation, the neointima in B-cell deficient recipients lacked SMCs. Post-transplantation administration of anti-donor serum to ,MT,/, recipients restored neointimal SMC population but did not influence the severity of TIH. Significant neointimal formation occurs in the absence of alloantibodies but lacks a SMC component. Therefore, SMC migration and proliferation is antibody dependent. [source]