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1.
J Clin Hypertens (Greenwich) ; 26(2): 155-165, 2024 02.
Article in English | MEDLINE | ID: mdl-38214206

ABSTRACT

Total neointima implantation (patch neointima technique + triple-branched stent graft placement) has been performed in proximal aortic repair for acute type A aortic dissection (ATAAD) for more than 10 years at a center. However, there is no report on the mid-term outcomes with a control group of the surgical procedure. Consequently, the authors aimed to evaluate the safety and efficacy of this technique in this study. Patients who underwent the total neointima implantation were classified as Group A, and those who underwent the conventional aortic root reconstruction with the "sandwich" technique and the total aortic arch replacement were classified as Group B. Furthermore, the authors described the preoperative characteristics, operative data, and patient outcomes. Group A patients experienced a shorter surgery duration, lower volumes of perioperative bleeding, and fewer red blood cell transfusions. The incidence of neurological complications was significantly reduced in Group A. All patients maintained a normal range of proximal aortic sizes after surgery. Kaplan-Meier analysis revealed no significant differences between the patients in the two groups regarding cumulative mortality and the incidence of moderate-to-severe aortic insufficiency. In well-selected patients, total neointima implantation is an alternative procedure for the surgical repair of ATAAD.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Dissection , Blood Vessel Prosthesis Implantation , Hypertension , Humans , Aortic Aneurysm, Thoracic/etiology , Aortic Aneurysm, Thoracic/surgery , Aorta, Thoracic/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/methods , Neointima/etiology , Neointima/surgery , Hypertension/etiology , Aortic Dissection/surgery , Stents , Treatment Outcome , Retrospective Studies
2.
Ann Thorac Surg ; 112(1): 75-82, 2021 07.
Article in English | MEDLINE | ID: mdl-33098877

ABSTRACT

BACKGROUND: The patch neointima technique is a modified valve-sparing aortic root repair surgery for acute type A aortic dissection and the short-term outcomes are satisfactory. The midterm outcomes have not been reported. METHODS: From January 2009 to December 2012, 147 patients underwent valve-sparing aortic root repair with the patch neointima technique for type A aortic dissection in our center. The midterm outcomes of the patients were evaluated by echocardiography and aortic computed tomography angiography. RESULTS: Of 147 patients, 32 patients (21.8%) underwent proximal arch repair, and 115 patients (78.2%) underwent proximal arch repair combined with triple-branched stent graft implantation. The perioperative mortality was 5.4%. Preoperative aortic insufficiency (AI) was observed in 94 patients (63.9%); 131 patients (89.1%) left the operating room with 0 AI; the remaining 16 patients (10.9%) had trace or less than 1+ AI. A total of 128 patients (87.1%) completed 7-year follow-up. The mean follow-up time was 5.7 ± 1.2 years. As many as 82% of patients (105) were 0 AI and 15.6% of patients (20) were 0.5+ trace or less than 1+ AI. No reoperation was performed for the aortic root. The diameters of sinotubular junction and sinus were reduced to the normal range (28.3 ± 4.2 mm and 30.5 ± 3.6 mm, respectively) and remained stable (28.9 ± 5.6 mm, P = .300, and 30.8 ± 4.2 mm, P = .540, respectively) during 7 years of follow-up. CONCLUSIONS: Valve-sparing aortic root repair with patch neointima technique was associated with stable function of the aortic valves and no expansion of the aortic root in the midterm.


Subject(s)
Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Neointima/surgery , Acute Disease , Adult , Aortic Dissection/diagnosis , Computed Tomography Angiography , Echocardiography , Female , Follow-Up Studies , Humans , Male , Neointima/diagnosis , Retrospective Studies , Time Factors , Treatment Outcome
3.
J Interv Cardiol ; 2019: 6515129, 2019.
Article in English | MEDLINE | ID: mdl-31772538

ABSTRACT

OBJECTIVES: We aimed to compare the results of neointimal modification before drug-coated balloon (DCB) treatment with excimer laser coronary atherectomy (ELCA) plus scoring balloon predilation versus scoring balloon alone in patients presenting with in-stent restenosis (ISR). BACKGROUND: Treatment of ISR with ELCA typically results in superior acute gain by neointima debulking. However, the efficacy of combination therapy of ELCA and DCB remains unknown. METHODS: A total of 42 patients (44 ISR lesions) undergoing DCB treatment with ELCA plus scoring balloon (ELCA group, n = 18) or scoring balloon alone (non-ELCA group, n = 24) were evaluated via serial assessment by optical coherence tomography (OCT) performed before, after intervention, and at 6 months. RESULTS: Although there was significantly greater frequency of diffuse restenosis and percent diameter stenosis (%DS) after intervention in the ELCA group, comparable result was shown in %DS, late lumen loss, and binary angiographic restenosis at follow-up. On OCT analysis, a decreased tendency in the minimum lumen area and a significant decrease in the minimum stent area were observed in the ELCA group between 6-month follow-up and after intervention (-0.89 ± 1.36 mm2 vs. -0.09 ± 1.25 mm2, p = 0.05, -0.49 ± 1.48 mm2 vs. 0.28 ± 0.78 mm2, p = 0.03, respectively). The changes in the neointimal area were similar between the groups, and target lesion revascularization showed comparable rates at 1 year (11.1% vs. 11.4%, p = 0.85). CONCLUSIONS: Despite greater %DS after intervention, ELCA before DCB had possible benefit for late angiographic and clinical outcome.


Subject(s)
Angioplasty, Balloon, Coronary , Atherectomy, Coronary , Coronary Angiography/methods , Coronary Restenosis , Neointima , Tomography, Optical Coherence , Aged , Angioplasty, Balloon, Coronary/adverse effects , Angioplasty, Balloon, Coronary/instrumentation , Angioplasty, Balloon, Coronary/methods , Atherectomy, Coronary/adverse effects , Atherectomy, Coronary/instrumentation , Atherectomy, Coronary/methods , Coronary Restenosis/diagnosis , Coronary Restenosis/surgery , Drug-Eluting Stents , Female , Humans , Japan/epidemiology , Lasers, Excimer/therapeutic use , Male , Neointima/diagnostic imaging , Neointima/etiology , Neointima/surgery , Outcome and Process Assessment, Health Care , Retrospective Studies , Time Factors , Tomography, Optical Coherence/methods , Tomography, Optical Coherence/statistics & numerical data
4.
Nagoya J Med Sci ; 81(2): 313-323, 2019 May.
Article in English | MEDLINE | ID: mdl-31239599

ABSTRACT

Neointimal calcification after stent implantation has been reported as one of the forms of neoatherosclerosis. There are a few patients with in-stent restenosis (ISR) and an undilatable calcified neointima who require rotational atherectomy to achieve sufficient acute gain in lumen diameter. However, the clinical outcomes of rotational atherectomy for undilatable calcified ISR have not been fully elucidated. Therefore, we investigated the safety and efficacy of rotational atherectomy for treating calcified ISR. This retrospective study included 17 patients (20 lesions) who had undergone percutaneous coronary intervention including rotational atherectomy to treat ISR with severely calcified neointima. Kaplan-Meier analysis was used to analyze the data. The mean age of the enrolled patients was 67±18 years, and 71% were men. The patients had highly atherogenic characteristics: 65% had diabetes mellitus and 53% were receiving hemodialysis. Procedural success was obtained in 19 (95%) patients, and the acute gain in lumen diameter was acceptable (1.7±0.6 mm). However, during a median follow-up of 571 days, the incidences of major adverse cardiac and cerebrovascular events per patient and clinical-driven target lesion revascularizations per lesion were relatively high. There were no differences in clinical outcomes according to the baseline characteristics, type of restenotic stents, and therapeutic strategy. In conclusion, clinical outcomes of rotational atherectomy for severely calcified ISR were unfavorable despite a high success rate and acceptable acute gain in lumen diameter.


Subject(s)
Atherectomy/methods , Coronary Restenosis/surgery , Drug-Eluting Stents/adverse effects , Aged , Aged, 80 and over , Humans , Kaplan-Meier Estimate , Middle Aged , Neointima/surgery , Retrospective Studies
5.
Int J Cardiol ; 258: 42-49, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29544956

ABSTRACT

BACKGROUND: Drug-eluting stents with biodegradable polymer coatings have shown promising outcomes in randomised studies. METHODS: We compared neointimal healing patterns including strut coverage and assessed neointimal maturity using a novel algorithm in coronary lesions treated with sirolimus-eluting stents with biodegradable polymer coating (BP-SES) or everolimus eluting stents with permanent polymer coating (PP-EES) using optical coherence tomography after 6months. RESULTS: A total of 39 patients were randomised to BP-SES (n=19) or PP-EES (n=20) for the treatment of coronary lesions. Of those, 29 patients (14 BP-SES and 15 PP-EES) underwent optical coherence tomography (OCT) and angiography at 6-month follow-up. Tissue coverage and apposition were assessed in a total of 6162 struts (BP-SES, n=2889; PP-EES, n=3273). Neointimal maturity was assessed in 3672 neointimal regions above struts using grey scale intensity analysis. OCT analysis showed neointimal coverage of 2433 (BP-SES) vs. 2702 (PP-EES) struts (84.2% vs. 82.6%, p=0.70), whereas the remainder was uncovered after 6months. Mean neointimal thickness did not differ significantly between groups (54.3±7.8µm vs. 80±14.6µm, p=0.12). The rate of malapposed struts was comparable between groups (1.3% vs. 2.2%, p=0.27). Grey scale signal intensity analysis showed mature tissue coverage of struts in 46.2% in BP-SES vs. 31.8% in PP-EES (p=0.31) of neointimal regions. CONCLUSION: The present study showed comparable early vascular healing response characterised by neointimal coverage with mainly immature neointima in both BP-SES and PP-EES.


Subject(s)
Absorbable Implants/trends , Coronary Artery Disease/surgery , Drug-Eluting Stents/trends , Polymers/administration & dosage , Sirolimus/administration & dosage , Tomography, Optical Coherence/trends , Aged , Aged, 80 and over , Coronary Artery Disease/diagnostic imaging , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neointima/diagnostic imaging , Neointima/surgery , Percutaneous Coronary Intervention/methods , Percutaneous Coronary Intervention/trends , Tomography, Optical Coherence/methods
6.
J Neurointerv Surg ; 10(11): 1097-1101, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29511117

ABSTRACT

BACKGROUND: Optical coherence tomography (OCT) is a high-resolution, intra-vascular diagnostic technique widely used for the characterization of vascular pathologies and optimization of stent implantation during percutaneous coronary intervention. OCT was used to investigate the in vivo vascular response to a new phosphorylcholine surface modified flow diverter (sPED). METHODS: In an in vivo rabbit aneurysmal model, we used two different types of flow diverters (classic Pipeline - cPED; and sPED) with or without dual antiplatelet therapy (four groups, n=10 per group). OCT cross-sectional area measurements were compared with histology in all animals. Neointimal hyperplasia (NIH) ratio was compared between OCT and histology at five different levels for each stent. The severity of NIH was also compared between the different stents, antiplatelet protocols, and vessel locations. RESULTS: OCT was used to calculate in-stent hyperplasia in 227 different locations corresponding to histology sections. OCT measurement strongly correlated with gold standard histology (r2=0.83; slope=0.988; P<0.0001). sPED had significantly less in-stent NIH than non-treated flow diverters (mean percent of lumen reduction 5.7% for sPED versus 8.9% for cPED; P<0.0001). The NIH ratio was slightly higher with dual antiplatelet therapy (DAPT) (NIH ratio=7.9% with DAPT versus 6.8% without DAPT; P<0.05). Complete and near complete occlusion rates of the aneurysms were not different with the cPED or sPED. CONCLUSION: OCT is a promising technique for immediate and long-term evaluation of flow diverter stent treatments. In an animal model, phosphorylcholine surface modified flow diverters induces less NIH after stent implant without reducing aneurysm occlusion rates.


Subject(s)
Intracranial Aneurysm/surgery , Neointima/surgery , Phosphorylcholine , Self Expandable Metallic Stents , Animals , Coronary Vessels , Endovascular Procedures/instrumentation , Endovascular Procedures/methods , Hyperplasia/diagnostic imaging , Hyperplasia/etiology , Intracranial Aneurysm/diagnostic imaging , Neointima/diagnostic imaging , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/methods , Rabbits , Random Allocation , Self Expandable Metallic Stents/adverse effects , Tomography, Optical Coherence/methods
7.
Cell Physiol Biochem ; 42(4): 1303-1312, 2017.
Article in English | MEDLINE | ID: mdl-28715799

ABSTRACT

BACKGROUND/AIMS: Neointimal formation following vascular injury remains a major mechanism of restenosis, whereas the precise sources of neointimal cells are still uncertain. We tested the hypothesis that both injured arterial cells and non-arterial cells contribute to intimal hyperplasia. METHODS: Following allograft transplantation of the balloon-injured carotid common artery (n = 3-6), the cellular composition of the transplant grafts and the origins of neointimal cells were measured by immunohistochemistry and immunofluorescence staining. RESULTS: Smooth muscle actin (SMA)-positive and CD68-positive cells were clearly observed 14 days later in the neointima after allograft transplantation of the balloon-injured carotid common artery, where re-endothelialization was not yet complete. Green fluorescent protein (GFP) and wild-type (WT) allograft transplantation revealed that the majority of the neointima cells were apparently from the recipient (≈85%) versus the donor (≈15%). Both monocyte chemotactic protein-1 (MCP-1)/CCR2 and stromal cell-derived factor-1 (SDF-1)/CXCR4 signaling were involved in intimal hyperplasia, with bone marrow-derived cells also playing a role. CONCLUSION: These data support the hypothesis that intimal hyperplasia could develop in our novel rat allograft transplantation model of arterial injury, where neointima is attributable not only to local arterial cells but also non-arterial cells including the bone marrow.


Subject(s)
Bone Marrow Cells/pathology , Carotid Artery Injuries/pathology , Carotid Artery, Common/pathology , Endothelial Cells/pathology , Neointima/pathology , Tissue Transplantation , Tunica Intima/injuries , Actins/genetics , Actins/immunology , Animals , Antigens, CD/genetics , Antigens, CD/immunology , Antigens, Differentiation, Myelomonocytic/genetics , Antigens, Differentiation, Myelomonocytic/immunology , Bone Marrow Cells/immunology , Carotid Artery Injuries/genetics , Carotid Artery Injuries/immunology , Carotid Artery Injuries/surgery , Carotid Artery, Common/immunology , Carotid Artery, Common/surgery , Cell Lineage/immunology , Cell Tracking , Chemokine CCL2/genetics , Chemokine CCL2/immunology , Chemokine CXCL12/genetics , Chemokine CXCL12/immunology , Endothelial Cells/immunology , Gene Expression Regulation , Genes, Reporter , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/immunology , Neointima/genetics , Neointima/immunology , Neointima/surgery , Rats , Rats, Inbred Lew , Rats, Transgenic , Receptors, CCR2/genetics , Receptors, CCR2/immunology , Receptors, CXCR4/genetics , Receptors, CXCR4/immunology , Signal Transduction , Transplantation, Homologous , Tunica Intima/immunology , Tunica Intima/surgery
8.
Cardiovasc Intervent Radiol ; 40(9): 1473-1476, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28386707

ABSTRACT

Transjugular intrahepatic portosystemic shunt (TIPS) dysfunction is conventionally managed with balloon angioplasty, stent extension, and sharp recanalization when necessary. We describe percutaneous transjugular recanalization and neointimal excision of a chronically occluded 17-year-old TIPS using excimer laser after conventional techniques were unsuccessful. Patient clinical improvement and shunt patency were documented three weeks post-intervention.


Subject(s)
Graft Occlusion, Vascular/surgery , Laser Therapy/methods , Lasers, Excimer/therapeutic use , Neointima/surgery , Portasystemic Shunt, Transjugular Intrahepatic/methods , Chronic Disease , Humans , Treatment Outcome
9.
Acta Biochim Biophys Sin (Shanghai) ; 49(3): 246-253, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-28159982

ABSTRACT

Reendothelialization in the aneurysm neck is pivotal to vascular repair for intracranial aneurysm after flow diverter (FD) implantation. Recombinant human stromal cell-derived factor 1α (rhSDF-1α) is a vital chemoattractant to stem cells and potentially facilitates reendothelialization. Here, we sought to investigate the therapeutic effects of intravenous administration of rhSDF-1α and uncover its potential mechanism for promoting aneurysm neck reendothelialization. Recombinant pET32a-186 plasmid was transformed into Escherichia coli to produce the rhSDF-1α protein with biological activity. FD was implanted into the elastase-induced saccular aneurysm in New Zealand white rabbits. rhSDF-1α (50 µg/kg/day) was intravenously administrated for consecutive 7 days after FD implantation. After these procedures, aneurysms were harvested after 2 or 4 weeks. Scanning electron microscopy was used to measure the neointima thickness and count the endothelial-like cells at aneurysm neck. Four weeks later, the mRNA levels of endothelial markers in the neointima at aneurysm neck were examined. Migration assay showed that rhSDF-1α could induce migration of endothelial progenitor cells in a dose-dependent manner. Two weeks after stent implantation, follow-up angiography showed partial aneurysm occlusion in one of each group and total aneurysm occlusion in 17 saccular aneurysm rabbits (9 of the rhSDF-1α group and 8 of the control group). No significant change of neointima thickness at aneurysm neck was observed. Intriguingly, more endothelial-like cells were observed at aneurysm neck in the rhSDF-1α group at 2 weeks (55 vs 13 cells per high-power field) and 4 weeks (104 vs 60 cells per high-power field). The mRNA levels of Tie-2, VE-cadherin, KDR and E-selectin were significantly enhanced compared with those of the control group. These results showed that intravenous administration of rhSDF-1α can accelerate reendothelialization in the aneurysm neck after FD implantation. Our study reveals an important role of rhSDF-1α in inducing aneurysm occlusion and suggests that it achieves its function through modulating the reendothelialization.


Subject(s)
Aneurysm/pathology , Chemokine CXCL12/administration & dosage , Endothelium, Vascular/pathology , Endovascular Procedures/instrumentation , Prosthesis Implantation/adverse effects , Recombinant Proteins/administration & dosage , Aneurysm/etiology , Aneurysm/metabolism , Aneurysm/surgery , Animals , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Humans , Male , Neointima/etiology , Neointima/metabolism , Neointima/pathology , Neointima/surgery , Rabbits
10.
EuroIntervention ; 12(12): 1551-1558, 2016 Dec 20.
Article in English | MEDLINE | ID: mdl-27998849

ABSTRACT

AIMS: This study sought to investigate differences in vascular response between self-expanding bare metal nitinol stents (BMS) and paclitaxel-eluting nitinol stents (PES), in superficial femoral artery (SFA) disease, using optical frequency domain imaging (OFDI). METHODS AND RESULTS: Six months after stent implantation, follow-up quantitative vascular angiography (QVA) and OFDI assessment were scheduled to evaluate vascular response. Volume index (VI) was defined as volume divided by stent length. The primary endpoint was OFDI-derived late lumen area loss, defined as lumen VI post stent implantation minus lumen VI at follow-up. A total of 28 SFA lesions were analysed, with cases randomised to receive either BMS or PES implantation. QVA-derived diameter stenosis at six-month follow-up was lower in the PES group than in the BMS group (28.5% vs. 39.7%, p=0.04). After six months, BMS VI increased by 33.8% (20.7±3.7 to 27.7±3.5 mm3/mm), whilst PES exhibited an increase of 32.1% (19.0±2.3 to 25.1±4.7 mm3/mm). Neointimal VI was smaller (7.4±2.6 mm3/mm vs. 10.5±3.2 mm3/mm, p<0.01) and late lumen area loss was lower (2.9±1.3 mm3/mm vs. 5.6±2.8 mm3/mm, p<0.01) in the PES group. CONCLUSIONS: Serial volumetric OFDI analyses confirmed significantly smaller amounts of neointimal tissue and lower late lumen area loss following PES implantation for SFA lesions at short-term follow-up.


Subject(s)
Alloys/therapeutic use , Drug-Eluting Stents , Femoral Artery/surgery , Neointima/surgery , Optical Imaging , Paclitaxel/therapeutic use , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neointima/diagnosis , Optical Imaging/methods , Ultrasonography, Interventional/methods
11.
EuroIntervention ; 11(14): e1619-26, 2016 Apr 08.
Article in English | MEDLINE | ID: mdl-25420791

ABSTRACT

AIMS: To compare tissue coverage in coronary lesions stented with durable fluoropolymer-coated everolimus-eluting stents (EES) vs. biodegradable polymer-coated biolimus A9-eluting stents (BES). METHODS AND RESULTS: Sixty-four patients (64 lesions) with de novo coronary artery lesions were randomised to percutaneous treatment with XIENCE EES (Abbott Vascular, Santa Clara, CA, USA) vs. BioMatrix BES (Biosensors, Morges, Switzerland). The primary endpoint was the percentage of uncovered struts, as assessed with OCT, at nine months. The average percentage of uncovered struts was significantly lower with EES (4.3±4.8% vs. 8.7±7.8% with BES, p=0.019). There was no difference in the average percentage of malapposed struts at baseline (6.8±6.9% vs. 6.9±7.0%, respectively, p=0.974) and at follow-up (0.1±0.3% vs. 0.6±1.3%, p=0.143). Neointimal thickness at nine months was 109±43 µm in EES vs. 64±18 µm in BES (p<0.001), and angiographic LLL was 0.15 mm in EES vs. 0.10 mm in BES (p=0.581). We did not observe differences in the incidence of MACE and ST. CONCLUSIONS: A significantly higher percentage of uncovered struts was detected in the BioMatrix BES compared with the XIENCE EES at nine-month follow-up. Our findings do not support a preferential use of stents with biodegradable polymer-based biolimus elution to reduce the risk for ST.


Subject(s)
Coronary Artery Disease/therapy , Coronary Restenosis/surgery , Coronary Vessels/surgery , Drug-Eluting Stents , Immunosuppressive Agents/therapeutic use , ST Elevation Myocardial Infarction/therapy , Adult , Aged , Aged, 80 and over , Coronary Restenosis/pathology , Coronary Vessels/pathology , Everolimus/therapeutic use , Female , Humans , Male , Middle Aged , Neointima/pathology , Neointima/surgery , Percutaneous Coronary Intervention/methods , Tomography, Optical Coherence/methods , Treatment Outcome
12.
Vascular ; 23(2): 124-31, 2015 Apr.
Article in English | MEDLINE | ID: mdl-24803551

ABSTRACT

PURPOSE: The effect of adenosine (9-ß-0-ribifuranosyladenine) on the endothelial cell proliferation and neointimal hyperplasia is investigated in the rabbit carotid artery anastomosis model. METHODS: Twenty-eight New Zealand white rabbits were arranged in four groups of seven animals each. The right carotid arteries of each animal were transsected and re-anastomosed. The left sides remained as control. In Group A, no medication was used. In Group B, subcutaneous Adenosine was applied for 3 days. In Group C, the same dose was applied for 7 days, and in Group D for 21 days. After 28 days, the luminal diameters, luminal areas, intima/media ratios were all measured by using histopathological evaluation. FINDINGS: The mean luminal diameters and areas of the four groups were smaller than the control ones. Massive thickening of smooth muscle cell proliferation and dense intensifying in the connecting tissues were observed most prominently in Group A, in decreasing degrees within other groups. Intima/media ratio was highest in Group A. Scoring the quantity of e-NOS positive staining also revealed a significant difference between the experimental groups and their control associates. CONCLUSION: The process of endothelial cell proliferation and neointimal hyperplasia can be significantly reduced by the use of adenosine.


Subject(s)
Adenosine/pharmacology , Carotid Arteries/surgery , Cell Proliferation/drug effects , Myocytes, Smooth Muscle/drug effects , Neointima/surgery , Tunica Intima/surgery , Anastomosis, Surgical/methods , Animals , Carotid Arteries/pathology , Disease Models, Animal , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Hyperplasia , Rabbits
13.
Pathol Res Pract ; 210(12): 1026-30, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24815534

ABSTRACT

Restenosis after stenting occurs secondary to the neointima formation. Neovessels have been found in the neointima within stents. However, there are few studies correlating neointimal angiogenesis and in-stent restenosis in humans. We analyzed 65 post-mortem stented arteries from 33 patients with duration >3 months. Cause of death was determined incidental to the coronary findings in every case. Stented segments were embedded in paraffin and stained immunohistochemically for CD68 (macrophages), and endothelial marker PECAM-1 (CD31). Computerized morphometry was performed to quantitate neovessel density for CD31, macrophage infiltrates, as well as plaque and neointimal area. In-stent restenosis was defined as luminal narrowing ≥ 75% cross-section of the stented area. Underlying plaque morphology was classified as fibrous or atheromatous. Neovessels were present in the neointima of 57 stented segments (88%). Mean neovessel density was greater in restenotic vs. non-restenotic neointimas (p = 0.009) and macrophage density was also greater (p = 0.006). Neointimal area correlated positively with density of neointimal vessels (p = 0.002), as well as neointimal macrophage density (p = 0.006), but not type of stent, underlying plaque type, or underlying plaque macrophage score. We conclude that in-stent restenosis is associated with neointimal angiogenesis which is accompanied by macrophage inflammation. The relevance of these findings to treatment and prevention of in-stent restenosis needs to be further explored.


Subject(s)
Coronary Restenosis/pathology , Coronary Vessels/pathology , Macrophages/pathology , Neointima/pathology , Neovascularization, Pathologic/pathology , Plaque, Atherosclerotic/pathology , Coronary Vessels/surgery , Female , Humans , Male , Neointima/surgery , Plaque, Atherosclerotic/surgery , Registries , Stents/adverse effects
14.
Cardiovasc Res ; 101(3): 454-63, 2014 Mar 01.
Article in English | MEDLINE | ID: mdl-24319016

ABSTRACT

AIMS: Cathepsin S (Cat S) is a potent lysosomal protease that is secreted into the extracellular space and has been implicated in elastin and collagen degradation in diseases such as atherosclerosis. Elastin degradation plays an important role in vascular remodelling. However, the mechanism by which Cat regulates this process and its contribution to vein graft remodelling remains unclear. METHODS AND RESULTS: Using a murine vein graft model, we examined the expression pattern of Cat family members. Expression of cathepsin genes was induced in vein grafts, with that of Cat S being the highest. Elevated Cat S expression was confirmed in both mouse and human vein grafts. To explore the role of Cat S, vein grafts were created between wild-type (WT) littermates and Cat S knockout (Cat S KO) mice. Knockout of Cat S in the recipients (vein(CatS-KO)-artery(CatS-KO) or vein(WT)-artery(CatS-KO)) significantly inhibited neointima formation and reduced the accumulation of macrophages and proliferation of smooth muscle cells in vein grafts. Knockout of Cat S preserved the elastic fibre integrity of vein grafts and inhibited the migration of macrophages across the elastin fibres. CONCLUSION: These results demonstrated that Cat S contributes to macrophage migration via degradation of elastic fibre integrity to facilitate neointima formation of vein grafts, which might provide a novel therapeutic target for preserving vein graft patency.


Subject(s)
Cathepsins/metabolism , Cell Movement , Elastic Tissue/pathology , Hyperplasia/metabolism , Macrophages/metabolism , Neointima/pathology , Animals , Cathepsins/genetics , Disease Models, Animal , Hyperplasia/pathology , Macrophages/cytology , Mice , Mice, Inbred C57BL , Mice, Knockout , Myocytes, Smooth Muscle/metabolism , Neointima/metabolism , Neointima/surgery , Signal Transduction/physiology , Veins/transplantation
15.
Circulation ; 128(11 Suppl 1): S50-S58, 2013 Sep 10.
Article in English | MEDLINE | ID: mdl-24030421

ABSTRACT

BACKGROUND: Endothelial cell (EC) survival and regeneration are important determinants of the response to vascular injury that leads to neointimal hyperplasia and accelerated atherosclerosis. Nitric oxide (NO) is a key regulator of EC and endothelial progenitor cell function, but the pathophysiological mechanisms that regulate endothelial NO synthase in endothelial regeneration remain unclear. METHODS AND RESULTS: Endothelium-targeted overexpression of GTP cyclohydrolase (GCH) I increased levels of the endothelial NO synthase cofactor, tetrahydrobiopterin, in an EC-specific manner and reduced neointimal hyperplasia in experimental vein grafts in GCH/apolipoprotein E-knockout mice. These effects were mediated through enhanced donor-derived survival and recipient-derived repopulation of GCH transgenic ECs, revealed by tracking studies in Tie2-LacZ/GCH-Tg/apolipoprotein E-knockout recipient mice or donor grafts, respectively. Endothelial GCH overexpression increased endothelial NO synthase coupling and enhanced the proliferative capacity of ECs and circulating endothelial progenitor cell numbers after vascular injury. CONCLUSIONS: These observations indicate that endothelial tetrahydrobiopterin availability modulates neointimal hyperplasia after vascular injury via accelerated EC repopulation and growth. Targeting tetrahydrobiopterin-dependent endothelial NO synthase regulation in the endothelium is a rational therapeutic target to enhance endothelial regeneration and reduce neointimal hyperplasia in vascular injury states.


Subject(s)
Biopterins/analogs & derivatives , Cell Survival/physiology , Endothelial Cells/physiology , Regeneration/physiology , Up-Regulation/physiology , Animals , Biopterins/physiology , Endothelial Cells/pathology , Humans , Hyperplasia/pathology , Hyperplasia/surgery , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Neointima/pathology , Neointima/surgery , Transplants , Vena Cava, Inferior/cytology , Vena Cava, Inferior/physiology
16.
Cardiovasc Revasc Med ; 13(6): 350-2, 2012.
Article in English | MEDLINE | ID: mdl-22898053

ABSTRACT

An increasing number of studies have reported intimal atherosclerotic changes, or neoatherosclerosis in the late phase after bare metal stent implantation, however, only a few reports have showed the presence of severe intimal calcification in a bare metal stent. We herein report a case of a 68-year-old male with severely calcified neointima occurring 9 years after the bare metal stent implantation. Pre-procedural coronary computed tomography angiography and peri-procedural intravascular ultrasound demonstrated severe calcification within the in-stent restenotic lesion. Although the pre-dilation balloon ruptured due to the calcification, the lesion was nevertheless successfully dilated with the stent. Calcified lesions often require complex techniques, and we therefore should be aware of the potential occurrence of a severely calcified neointima in coronary stents, and performing coronary computed tomography angiography in advance is a great help for performing effective coronary intervention.


Subject(s)
Atherosclerosis/surgery , Coronary Restenosis/pathology , Metals/adverse effects , Neointima/surgery , Stents/adverse effects , Vascular Calcification/surgery , Aged , Atherosclerosis/diagnosis , Coronary Angiography/methods , Coronary Restenosis/diagnostic imaging , Humans , Male , Neointima/diagnostic imaging , Treatment Outcome , Ultrasonography, Interventional/methods
17.
J Vasc Surg ; 55(5): 1338-44; discussion 1344-5, 2012 May.
Article in English | MEDLINE | ID: mdl-22459751

ABSTRACT

OBJECTIVE: We report the midterm results of external iliac artery reconstruction in 25 high-performance cyclists. METHODS: Cyclists undergoing arterial reconstruction for symptomatic external iliac arteriopathy at a single institution between October 2004 and August 2010 were identified. With Institutional Review Board approval, data were collected from medical record review and telephone interview. Results were analyzed with χ(2) or independent t-test. RESULTS: Twenty-five patients (31 limbs) underwent operation, which included arterial reconstruction with or without inguinal ligament release. The average patient age at operation was 43.8 ± 5.0 for graft and 35.1 ± 1.9 for patch (P = .08). The average time from competitive cycling until operation was 18.2 ± 5.8 years for graft and 20.0 ± 2.5 for patch repairs (NS). Patients included 14 males and 11 females. There were 23 unilateral and four bilateral arterial reconstructions, including 26 patch angioplasties for localized disease and five interposition grafts for extensive disease; three patients underwent contralateral reconstruction as a separate procedure. Concomitant ipsilateral inguinal ligament release was performed in 25 patients (28 limbs), with contralateral release done in 12 patients (12 limbs). Three patients with isolated ligament release required subsequent arterial intervention. Follow-up averaged 32 months (range, 2-74). Primary patency for all reconstructions was 100%; the four reoperations (five limbs; one bilateral) were for symptom recurrence, two postgraft and two postangioplasty. Three reoperations were for recurrent intimal hyperplasia, one for disease distal to the anastomosis, and one for concomitant atherosclerotic disease. Based on available data, postexercise ankle-brachial indices were improved in 18 of 23 limbs. Seventeen patients completed questions regarding satisfaction: 10 were satisfied or very satisfied (zero graft, 10 patch; P = .25), while four were unsatisfied (three graft, two patch; P = .017, including one patient with both a patch and graft repair). All 20 patients for whom follow-up data were available are still cycling, 10 competitively. Two of the four reoperated patients were unsatisfied; all four are still cycling, one competitively. CONCLUSIONS: External iliac arteriopathy is a disease of prolonged, sustained, and repetitive trauma. Patch angioplasty yields a low rate of reoperation, more satisfied patients, return to competitive activity, and improvement in postexercise ankle-brachial indices. Interposition grafting is associated with slightly older patients, more extensive disease, and less satisfying results. Intimal hyperplasia is the most frequent complication necessitating reoperation. Both the decision to pursue arterial reconstruction and patient expectations must be tempered by the pattern of disease and the potential for unsatisfactory results.


Subject(s)
Angioplasty , Bicycling/injuries , Blood Vessel Prosthesis Implantation , Iliac Artery/surgery , Vascular Surgical Procedures , Vascular System Injuries/surgery , Adult , Ankle Brachial Index , Chi-Square Distribution , Endarterectomy , Female , Humans , Iliac Artery/injuries , Iliac Artery/physiopathology , Kaplan-Meier Estimate , Male , Middle Aged , Neointima/etiology , Neointima/surgery , Patient Satisfaction , Recovery of Function , Reoperation , Retrospective Studies , Time Factors , Treatment Outcome , Vascular Patency , Vascular Surgical Procedures/adverse effects , Vascular System Injuries/diagnosis , Vascular System Injuries/etiology , Vascular System Injuries/physiopathology , Virginia , Young Adult
18.
Cardiovasc Intervent Radiol ; 35(2): 418-21, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21904810

ABSTRACT

In-stent reocclusion is a frequent complication of endovascular treatment and stenting, especially in the superficial femoral artery. Neointimal hyperplasia is the main cause of this problem, but in many cases, it occurs as a result of the presence of stent strut fractures. The two treatment options are endovascular and surgical intervention. The effectiveness of endovascular interventions in patients with critical limb ischemia has been well established, but in some cases, crossing the occluded stent is difficult. We describe a new technique to recanalize long in-stent superficial femoral artery occlusions characterized by direct stent puncture, followed by retrograde-antegrade recanalization after antegrade failures.


Subject(s)
Arterial Occlusive Diseases/therapy , Endovascular Procedures/methods , Femoral Artery/surgery , Stents/adverse effects , Aged , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/etiology , Femoral Artery/diagnostic imaging , Follow-Up Studies , Humans , Male , Neointima/etiology , Neointima/surgery , Popliteal Artery/diagnostic imaging , Radiography , Treatment Outcome , Ultrasonography , Vascular Patency
19.
Chin Med J (Engl) ; 124(24): 4286-92, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22340401

ABSTRACT

BACKGROUND: Recent studies indicate that bone marrow-derived cells may significantly contribute to atherosclerosis, post-angioplasty restenosis and transplantation-associated vasculopathy. The responsible bone marrow (BM) cells and mechanisms regulating the mobilization of these cells are currently unclear. The purpose of this study was to investigate the expression of granulocyte colony-stimulating factor (G-CSF) on injured arteries and its effects on mesenchymal stem cells (MSCs) differentiation into vascular smooth muscle cells (VSMCs) in the process of vascular remodeling. METHODS: Balloon-mediated vascular injury was established in female rats (n = 100) which received radioprotective whole female BM cells by tail vein injection and male MSCs through a tibial BM injection after lethal irradiation. The injured and contralateral carotid arteries were harvested at 3, 7, 14 and 28 days after treatment. RESULTS: Morphometric analysis indicated that intima to media area-ratio (I/M ratio) significantly increased at 28 days, 0.899 ± 0.057 (P < 0.01), compared with uninjured arteries. Combining fluorescence in situ hybridization (FISH) and immunohistochemical analysis showed that a significant number of the neointimal cells derived from MSCs, (45.2 ± 8.5)% at 28 days (P = 0.01), compared with (23.5 ± 6.3)% at 14 days. G-CSF was induced in carotid arteries subject to balloon angioplasty (fold mRNA change = 8.67 ± 0.63 at three days, relative G-CSF protein = 0.657 ± 0.011 at three days, P < 0.01, respectively, compared with uninjured arteries). G-CSF was chemotactic for MSCs but did not affect the differentiation of MSCs into smooth-muscle-like cells. CONCLUSION: Increased expression of G-CSF by injured arteries plays an essential role in contribution to recruitment and homing of MSCs to the site of the arterial lesion.


Subject(s)
Granulocyte Colony-Stimulating Factor/metabolism , Mesenchymal Stem Cells/cytology , Vascular System Injuries/surgery , Vascular System Injuries/therapy , Angioplasty, Balloon , Animals , Blotting, Western , Carotid Arteries/surgery , Cell Differentiation , Cell Movement , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Female , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , Myocytes, Smooth Muscle/cytology , Neointima/surgery , Neointima/therapy , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction
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