OBJECTIVETo investigate the effect of bone marrow derived endothelial cells implantation on healing of acute injured intima.

METHODSMononuclear cells derived from bone marrow were differentiated to endothelial cells. The cells were labeled with bromodeoxyuridine. Carotids injuring was induced by a balloon in 40 rabbits, endothelial cell suspension (2 x 10(6)/ml, n = 20) or PBS (2 ml, n = 20) was infused to injured arteries. The intima covered area was tested by Evan's Blue staining. The average intima thickness and media thickness were observed 7 and 14 days post procedure by histological assay. The immunofluorescent staining was performed for testing the BrdU labeled-cells, and these cells were detected under a fluorescent microscope.

RESULTSIntima covered area rate was significant higher (54.1% +/- 8.2% vs. 30.0% +/- 5.5% at day 7, and 81.8% +/- 6.0% vs. 63.6% +/- 8.4% at day 14, all P < 0.05) and the intima thickness and media thickness were significantly reduced in the endothelial cell suspension group.

CONCLUSIONThe bone marrow derived endothelial cell promoted healing post intima injury in this model compared to PBS group (all P < 0.05).

Animals ; Bone Marrow Cells ; cytology ; Bone Marrow Transplantation ; Carotid Arteries ; pathology ; Carotid Artery Injuries ; pathology ; surgery ; Endothelial Cells ; cytology ; pathology ; transplantation ; Female ; Male ; Rabbits ; Transplantation, Autologous

OBJECTIVETo investigate the in vivo gene expression of adenovirus-mediated human tissue factor pathway inhibitor (hTFPI) and its inhibition effects on intimal proliferation in rabbit carotid arteries after balloon injury.

METHODSRabbits underwent carotid artery balloon injuries were treated with Ad-TFPI (n = 25), Ad-LacZ (n = 25) or PBS (n = 10), respectively. Sham operated rabbits (n = 10) serve as normal controls. The expressions of human TFPI at mRNA and protein levels were detected by RT-PCR and ELISA respectively on the 3rd, 7th, 10th, 14th, 28th day after operation. Intimal proliferation was detected by angiograms and morphometric analysis.

RESULTSTFPI mRNA and protein expressions were detected at 3 days and peaked at the 10th and 14th day after TFPI gene transfer. The expressions were still detectable on the 28th day. There was no TFPI expression in Ad-LacZ group. The carotid angiogram results indicated that the minimal lumen diameter in TFPI group was significantly larger and the lumina stenosis percentage was significantly lower in TFPI group compared those in Ad-LacZ and PBS groups (all P < 0.05). The morphometric analysis showed that the intimal area, the ratio of the intimal/media area, the lumina stenosis percentage in TFPI group were all significantly reduced compared with those in Ad-LacZ and PBS groups (all P < 0.01).

CONCLUSIONSThe TFPI gene could be effectively transferred by adenovirus vector to injured carotid arteries and transferred Ad-TFPI could significantly attenuate intimal proliferation in balloon injured carotid arteries in rabbits.

Adenoviridae ; genetics ; Animals ; Carotid Arteries ; metabolism ; Carotid Artery Injuries ; metabolism ; pathology ; Female ; Gene Transfer Techniques ; Genetic Vectors ; Humans ; Lipoproteins ; genetics ; Male ; Rabbits ; Transfection ; Tunica Intima ; pathology

Epistaxis is commonly encountered in otorhinolaryngologic practice. However, severe and recurrent epistaxis is rarely seen, especially that originating from a pseudoaneurysm of the intracavernous internal carotid artery (ICA). We herein present the case of a 32-year-old man who was involved in a motor vehicle accident and subsequently developed recurrent episodes of profuse epistaxis for the next three months, which required blood transfusion and nasal packing to control the bleeding. Computed tomography angiography revealed a large intracavernous ICA pseudoaneurysm measuring 1.7 cm × 1.2 cm × 1.0 cm. The patient underwent emergent four-vessel angiography and coil embolisation and was discharged one week later without any episode of bleeding. He remained asymptomatic after three-month and one‑year intervals. This case report highlights a large intracavernous ICA pseudoaneurysm as a rare cause of epistaxis, which requires a high index of suspicion in the right clinical setting and emergent endovascular treatment to prevent mortality.
Accidents, Traffic ; Adult ; Aneurysm, False ; diagnostic imaging ; etiology ; surgery ; Carotid Artery Injuries ; Carotid Artery, Internal ; diagnostic imaging ; pathology ; surgery ; Coronary Angiography ; methods ; Embolization, Therapeutic ; Epistaxis ; etiology ; Humans ; Male ; Tomography, X-Ray Computed

OBJECTIVETo observe the preventive effect of Radix Paeoniae Rubra (RPR) to restenosis after carotid balloon injury in rabbits.

METHODSThe rabbit model of carotid balloon injury was established adopting Clowes method, and treated with extract of RPR. Component of new genesic intima and expression of proliferating cell nuclear antigen (PCNA) and macrophage was determined by immunochemical stain. The collagen of type I was detected by special staining for blood vessels and the area of new genesic intima was measured by image assay system.

RESULTSRPR could remarkably decreased the PCNA positive expression and inhibit the proliferation of collagen type I and reduce the generating of new intima.

CONCLUSIONRPR has significant preventive effect on the restenosis after carotid ballon injury in high fat-diet induced atherosclerotic rabbits.

Angioplasty, Balloon ; adverse effects ; Animals ; Arteriosclerosis ; etiology ; pathology ; therapy ; Carotid Artery Injuries ; etiology ; Carotid Artery, Common ; pathology ; Carotid Stenosis ; etiology ; pathology ; therapy ; Drugs, Chinese Herbal ; pharmacology ; Hypercholesterolemia ; complications ; Muscle, Smooth, Vascular ; pathology ; Paeonia ; Proliferating Cell Nuclear Antigen ; metabolism ; Rabbits ; Secondary Prevention

Actins ; metabolism ; Animals ; Antigens, CD ; metabolism ; Cadherins ; metabolism ; Carotid Artery Injuries ; metabolism ; pathology ; Endothelium, Vascular ; metabolism ; ultrastructure ; Fluorescent Antibody Technique ; Microscopy, Confocal ; Rats ; Troponin ; metabolism

OBJECTIVETo observe the preventive and therapeutic effect of tanshinone (TA) on artery restenosis in the rat carotid injury model and explor the mechanism.

METHODMale SD rats were randomly divided into model control group, and low dose, moderate dose and high dose TA groups. Each group had 10 rats. The rats in the high, moderate and low dose groups were respectively fed with TA 120, 40,13.3 mg x kg(-1) x d(-1) by gast rogavage; the rats in the model control group were fed with the same volume solvent. Two days later, the rat's right carotid artery was injuried by balloon dilatation to induce intimal thickening for establishing the restenosis model. After 2 weeks of treatment, the artery was harvested and stained by hematoxylin-elsin (HE) and immunohistochemistry of PCNA, NF-kappaB and iNOS. The morphological changes were checked under microscope. The area of the intimal and medial layer of the vessels, and their ratios were analyzed with image analysis software. The expression level of PCNA, NF-kappaB and iNOS were used as the positive index.

RESULTThe intimal area and intima-to-media ratio of the injuried artery increased obviously, suggesting the model was successful. Compared with the model group, TA significantly decreased the intimal area and intima-to-media ratio (P < 0.05), and also decreased the positive index of PCNA and the positive ratio of NF-kappaB and iNOS (P < 0.05).

CONCLUSIONTA can effectively inhibit intimal thickening and inflammation. This result suggestes that TA may play a positive role in the prevention of restenosis after PTCA.

Angioplasty, Balloon, Coronary ; adverse effects ; Animals ; Carotid Artery Injuries ; complications ; Carotid Artery, Common ; metabolism ; pathology ; Carotid Stenosis ; etiology ; metabolism ; pathology ; Diterpenes, Abietane ; Male ; NF-kappa B ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Phenanthrenes ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Proliferating Cell Nuclear Antigen ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry ; Tunica Intima ; metabolism ; pathology

OBJECTIVETo investigate the role of small G-protein RhoA in neointimal formation following rat carotid artery balloon injury and related mechanisms.

METHODSMale 3-4-month-old Sprague-Dawley rats were used in the present study (10 rats per group). Group A: control; Group B: carotid artery balloon injury; Group C: injury + Ad-CMV-eGFP + Pluronic F-127; Group D: injury + Ad-CMV-N19RhoA-eGFP + Pluronic F-127; Group E: non injury + Ad-CMV-eGFP + Pluronic F-127. Perivascular gene transfer of an adenovirus co-expressing N19RhoA was performed to rat carotid artery following balloon injury and the effect on neointimal formation and the expressions of PCNA and α-SM-actin examined. Rats were killed after 14 days.

RESULTSThe protein expression of RhoA in group B was significantly higher than in group A (P = 0.001), and the positive cells rate of PCNA and α-SM-actin which were assessed by immunohistochemistry in group C (45.2% and 75.6%) was significantly higher than in group D (28.4% and 51.9%, all P < 0.01). The area of neointima was significantly smaller [(0.14 ± 0.08) mm(2) vs. (0.23 ± 0.10) mm(2), P < 0.01], the luminal area was significantly larger [(0.47 ± 0.11) mm(2) vs. (0.31 ± 0.06) mm(2), P < 0.01] in group D than in group C.

CONCLUSIONGene transfer of N19RhoA attenuates neointimal formation after balloon injury in rat carotid arteries possibly related to the modulating capacities of small G-protein RhoA on the proliferation, phenotypic differentiation and migration of vascular adventitial fibroblasts.

Adenoviridae ; genetics ; Animals ; Carotid Arteries ; metabolism ; Carotid Artery Injuries ; metabolism ; pathology ; Genetic Vectors ; Male ; Muscle, Smooth, Vascular ; metabolism ; Neointima ; Rats ; Rats, Sprague-Dawley ; Transfection ; rhoA GTP-Binding Protein ; genetics

OBJECTIVEThis study was aimed to investigate the effects of carbon monoxide releasing molecule (CORM-2), a novel carbon monoxide carrier, on the reendothelialization of carotid artery in rat endothelial denudation model.

METHODSMale rats subjected to carotid artery balloon injury were treated with CORM-2, inactive CORM-2 (iCORM-2) or dimethyl sulfoxide (DMSO). The reendothelialization capacity was evaluated by Evans Blue dye and the immunostaining with anti-CD31 antibody. The number of circulating endothelial progenitor cells (EPCs) was detected by flow cytometry. The proliferation, migration, and adhesion of human umbilical vein endothelial cells (HUVECs) were assessed by using [3H]thymidine, Boyden chamber and human fibronectin respectively. The expressions of protein were detected by using western blot analysis.

RESULTSCORM-2 remarkably accelerated the re-endothelialization 5 d later and inhibited neointima formation 28 d later. In addition, the number of peripheral EPCs significantly increased in CORM-2-treated rats than that in iCORM-2 or DMSO-treated rats after 5 d later. In vitro experiments, CORM-2 significantly enhanced the proliferation, migration and adhesion of HUVECs. The levels of Akt, eNOS phosphorylation, and NO generation in HUVECs were also much higher in CORM-2 treated group. Blocking of PI3K/Akt/eNOS signaling pathway markedly suppressed the enhanced migration and adhesion of HUVECs induced by CORM-2.

CONCLUSIONCORM-2 could promote endothelial repair, and inhibit neointima formation after carotid artery balloon injury, which might be associated with the function changes of HUVECs regulated by PI3K/Akt/eNOS pathway.

Animals ; Carbon Monoxide ; metabolism ; pharmacology ; Carotid Artery Injuries ; drug therapy ; immunology ; metabolism ; pathology ; Carotid Artery, Common ; drug effects ; immunology ; metabolism ; pathology ; Cell Adhesion ; drug effects ; Disease Models, Animal ; Endothelial Cells ; drug effects ; immunology ; metabolism ; pathology ; Endothelium, Vascular ; drug effects ; metabolism ; pathology ; Humans ; Male ; Rats ; Rats, Sprague-Dawley

The aims of the present study were to determine the effects of heparin-derived oligosaccharides (HDOs) on vascular intimal hyperplasia (IH) in balloon-injured carotid artery and to elucidate the underlying mechanisms of action. An animal model was established by rubbing the endothelia within the common carotid artery (CCA) in male rabbits. The rabbits were fed a high-cholesterol diet. Arterial IH was determined by histopathological changes to the CCA. Serum lipids were detected using an automated biochemical analysis. Expressions of mRNAs for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), scavenger receptor class B type I (SR-BI), and ATP-binding cassette transporter A1 (ABCA-1) were analyzed using reverse transcription polymerase chain reaction assays. Expressions of VEGF, VCAM-1, MCP-1, SR-BI and ABCA-1 proteins were analyzed by Western blotting. Enzyme-linked immunosorbent assays were used to quantify expression levels of VEGF and bFGF. Our results showed that administration of HDO significantly inhibited CCA histopathology and restenosis induced by balloon injury. The treatment with HDOs significantly decreased the mRNA and protein expression levels of VEGF, bFGF, VCAM-1, MCP-1, and SR-BI in the arterial wall; however, ABCA-1 expression level was elevated. HDO treatment led to a reduction in serum lipids (total cholesterol, triglycerides, high-density and low-density lipoproteins). Our results from the rabbit model indicated that HDOs could ameliorate IH and underlying mechanism might involve VEGF, bFGF, VCAM-1, MCP-1, SR-BI, and ABCA-1.
ATP Binding Cassette Transporter 1 ; analysis ; Animals ; Carotid Artery Injuries ; drug therapy ; pathology ; Chemokine CCL2 ; analysis ; Heparin ; therapeutic use ; Hyperplasia ; Male ; Oligosaccharides ; therapeutic use ; Rabbits ; Tunica Intima ; pathology ; Vascular Cell Adhesion Molecule-1 ; analysis ; Vascular Endothelial Growth Factor A ; analysis

This study evaluated the effects of adenovirus vector mediated human vascular endothelial growth factor-165 (hVEGF165) gene on prevention of restenosis after angioplasty. Rabbit models of bilateral carotid artery injury were established by balloon denudation. The recombinant adenoviruses containing hVEGF165 cDNA was directly injected into left side of the injured carotid arteries. On day 3 and week 3 after transfection the expression of VEGF was observed by RT-PCR and immunohistochemistry. The thrombokinesis, reendothelialization (rET) and intimal hyperplasia in carotid arteries were evaluated by computerized image analysis system 3 weeks after gene transfer. The changes in the VEGF gene-treated side were compared with the control side. Our results showed that 3 days and 3 weeks after hVEGF165 gene transfer the VEGF mRNA and antigen expression were detected in vivo. 3 weeks after the transfer, the carotid artery rET was markedly better in the VEGF gene-treated group compared with the control. The thrombokinesis, intima area/media area (I/M), maximal intimal and medial thicknesses (ITmax and MTmax) demonstrated a statistically significant decrease in arteries treated with VEGF gene as compared with the control group. It is concluded that VEGF gene transfer could be achieved by intra-arterial injection of recombinant adenoviruses. It might accelerate the restoration of endothelial integrity, inhibit thrombokinesis and attenuate intimal hyperplasia in the injured arteries after VEGF gene transfer. This procedure could be useful in preventing restenosis after angioplasty.
Adenoviridae ; genetics ; metabolism ; Angioplasty, Balloon ; adverse effects ; Animals ; Carotid Artery Injuries ; pathology ; Carotid Stenosis ; physiopathology ; prevention & control ; Cell Division ; drug effects ; Endothelium, Vascular ; injuries ; pathology ; Genetic Therapy ; Hyperplasia ; prevention & control ; Male ; Muscle, Smooth, Vascular ; cytology ; RNA, Messenger ; biosynthesis ; genetics ; Rabbits ; Recombination, Genetic ; Transfection ; methods ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics