Optical coherence tomography （OCT） is a new imaging modality with resolution of approximately 10 pm and can be employed to visualize intracoronary characteristics. Sirolimus-eluting stents （SES） are susceptible to...Optical coherence tomography （OCT） is a new imaging modality with resolution of approximately 10 pm and can be employed to visualize intracoronary characteristics. Sirolimus-eluting stents （SES） are susceptible to late thrombosis due to delayed reendothelialization over the stent struts, which may result in acute myocardial infarction or death. This study was designed to evaluate the re-endothelialization and neointimal coverage of SES with OCT 6 months and 12 months after implantation.Methods A total of 36 patients enrolled in the study underwent OCT examination 6 months （17 patients） and 12 months （19 patients） after SES implantation, The strut apposition to the vessel wall and neointimal coverage on SES struts were evaluated by OCT, Results Forty-six SES and 6561 struts were analyzed, At 6 months, 3041 struts （98.7%） were well-apposed and 39 struts （1,3%） were malapposed, At 12 months, 3434 struts （98,6%） were well-apposed and 47 struts （1,4%） were malapposed, Furthermore, only 4 SES at 6 months （18,2%） and 10 SES at 12 months （41,7%） were fully covered by neointimal growth, The average neointimal thicknesses covering the analyzed struts at 6 months and 12 months were （42±28） μm and （88±32） μm, respectively, There were 1989 struts at 6 months （72,1%） and 1461 struts at 12 months （45,6%） with neointimal thickness 〈100 μm, Conclusions OCT was able to visualize the strut apposition to the vessel wall and neointimal coverage on SES struts, At 6-month and 12-month follow-up examinations most struts were covered with thin neointima, but few of the entire SES showed full coverage. To prevent late-stent thrombosis in the presence of uncovered stent struts, longer dual antiplatelet drugs therapy should be recommended,展开更多
Percutaneous coronary intervention （PCI） with drug-eluting stent implantation has been provedefficient to reduce complications and restenosis in type B2/C lesions compared with bare stent, since the major drawback o...Percutaneous coronary intervention （PCI） with drug-eluting stent implantation has been provedefficient to reduce complications and restenosis in type B2/C lesions compared with bare stent, since the major drawback of the latter technique is intimal hyperplasia from the vessel media, which significantly cause in-stent restonosis. Despite the beneficial effects on the renin-angiotensin-aldosterone （RAAS） system, the role of angiotensin-converting enzyme （ACE） inhibitors after PCI is still unclear. However, first results of angiotensin receptor antagonist （valsartan） after stent implantation in the VaI-PREST1 and VALVACE2 trials have indicated the systemic pharmacological effect in the prevention of in-stent-restenosis. Up to our knowledge, whether local treatment of valsartan by implanting drug-eluting stent can generally prevent restenosis by inhibiting intimal hyperplasia has not been explored.展开更多
目的应用光学相干断层成像（OCT）技术比较冠状动脉内雷帕霉素药物洗脱支架（DES）和金属裸支架（BMS）治疗后内膜增殖情况.方法对19例冠心病经冠状动脉内支架置入治疗后5～93个月的患者进行冠状动脉造影复查,造影后对21支血管23个支架...目的应用光学相干断层成像（OCT）技术比较冠状动脉内雷帕霉素药物洗脱支架（DES）和金属裸支架（BMS）治疗后内膜增殖情况.方法对19例冠心病经冠状动脉内支架置入治疗后5～93个月的患者进行冠状动脉造影复查,造影后对21支血管23个支架进行OCT成像检查.DES术后6～10个月为药物支架A组;BMS术后5～10个月为金属裸支架B组;BMS术后23～93个月为金属裸支架C组.应用OCT成像技术比较3组支架之间内膜增殖情况.结果 OCT成像结果显示3组之间有关支架后最大内膜增殖厚度、血管腔直径和截面积丢失及直径和截面积再狭窄等方面差异有统计学意义.其中A组内膜最大增殖厚度明显小于B组（0.20 mm±0.13 mm vs 0.81 mm±0.46 mm,P=0.019）和C组（0.91 mm±0.27 mm,P=0.007）; A组血管腔直径丢失明显小于B组（0.27 mm ±0.17 mm vs 1.12 mm±0.79 mm,P=0.009）和C组（1.20 mm±0.31 mm P=0.013）;A组直径再狭窄明显小于B组（8%±4% vs 36%±24%, P=0.009）和C组（35%±6%,P=0.017）;A组截面积丢失明显小于B组（1.14 mm2 ±0.9 mm2 vs 3.96 mm2±2.62 mm,P=0.009）和C组（4.66 mm2±1.66 mm2,P=0.006）;A组截面积再狭窄明显小于B组（P=0.017）和C组（P=0.009）.置入的13个BMS支架,几乎所有支架支撑杆表面均有内膜覆盖,而置入DES后内膜增殖较少,部分支架支撑杆表面即使在支架术后29个月仍然没有内膜覆盖.结论 OCT成像技术可清晰地显示支架支撑杆及表面内膜增殖情况,对评价药物洗脱支架的治疗效果具有重要意义.展开更多
Background： Endothelial cell damage is an important pathophysiological step of restenosis after angioplasty and stenting. Cell transplantation has great therapeutic potential for endothelial recovery. We investigated...Background： Endothelial cell damage is an important pathophysiological step of restenosis after angioplasty and stenting. Cell transplantation has great therapeutic potential for endothelial recovery. We investigated the effect of transplanting endothelial progenitor cells （EPCs） derived from human early fetal aortas in rat injured arteries. Methods： The carotid arterial endothelium of Sprague-Dawley rats was damaged by dilatation with a 1.5 F balloon catheter, and then EPCs derived from human early fetal aortas （〈14 weeks） were injected into the lumen of the injured artery in transplanted rats, with an equal volume of normal saline injected into control rats. Rats were sacrificed at 2 and 4 weeks after treatment and transplanted cells were identified by immunohistochemical staining with anti-human CD31 and anti-human mitochondria antibodies. Arterial cross-sections were analyzed by pathology, immunohistochemistry, and morphometry. Results： Green fluorescence-labeled EPCs could be seen in the endovascular surface of balloon-injured vessels after transplantation. The intimal area and intimal/medial area ratio were significantly smaller in the transplanted group than in the control （P 〈 0.05） and the residual lumen area was larger （P 〈 0.05）. After EPC transplantation, a complete vascular endothelial layer was formed, which was positive for human yon Willebrand factor after immunohistochemical staining, and immunohistochemical staining revealed many CD31- and mitochondria-positive cells in the re-endothelialized endothelium with EPC transplantation but not control treatment. Conclusion： EPCs derived from human early fetal aorta were successfully transplanted into injured vessels and might inhibit neointimal hyperplasia after vascular injury.展开更多
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 ...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.展开更多
AIM: To study the genesis of neointima formation in pulmonary hypertension(PH), we investigated the role of caveolin-1 and related proteins. METHODS: Male Sprague Dawley rats were given monocrotaline(M, 40 mg/kg) or s...AIM: To study the genesis of neointima formation in pulmonary hypertension(PH), we investigated the role of caveolin-1 and related proteins. METHODS: Male Sprague Dawley rats were given monocrotaline(M, 40 mg/kg) or subjected to hypobaric hypoxia(H) to induce PH. Another group was given M and subjected to H to accelerate the disease process(M + H). Right ventricular systolic pressure, right ventricular hypertrophy, lung histology for medial hypertrophy and the presence of neointimal lesions were examined at 2 and 4 wk. The expression of caveolin-1 and its regulatory protein peroxisome proliferator-activated receptor(PPAR) γ, caveolin-2, proliferative and antiapoptotic factors(PY-STAT3, p-Erk, Bcl-x L), endothelial nitric oxide synthase(e NOS) and heat shock protein(HSP) 90 in the lungs were analyzed, and the results from M + H group were compared with the controls, M and H groups. Double immunofluorescence technique was used to identify the localization of caveolin-1 in pulmonary arteries in rat lungs and in human PH lung tissue. RESULTS: In the M + H group, PH was more severe compared with M or H group. In the 4 wk M+H group, several arteries with reduced caveolin-1 expression in endothelial layer coupled with an increased expression in smooth muscle cells(SMC), exhibited neointimal lesions. Neointima was present only in the arteries exhibiting enhanced caveolin-1 expression in SMC. Lung tissue obtained from patients with PH also revealed neointimal lesions only in the arteries exhibiting endothelial caveolin-1 loss accompanied by an increased caveolin-1 expression in SMC. Reduction in e NOS and HSP90 expression was present in the M groups(2 and 4 wk), but not in the M + H groups. In both M groups and in the M + H group at 2 wk, endothelial caveolin-1 loss was accompanied by an increase in PPARγ expression. In the M + H group at 4 wk, increase in caveolin-1 expression was accompanied by a reduction in the PPARγ expression. In the H group, there was neither a loss of endothelial caveolin-1, eNOS or HSP 90, nor展开更多
Objective Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts(AVGs),but the factors mediating this process are unclear.The purpose of this study was to investigate th...Objective Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts(AVGs),but the factors mediating this process are unclear.The purpose of this study was to investigate the role of endoplasmic reticulum stress(ERS)-induced endothelial dysfunction in neointima formation following AVGs in high-fat diet(HFD)mice.Methods CCAAT-enhancer-binding protein-homologous protein(CHOP)knockout(KO)mice were created.Mice were fed with HFD to produce HFD model.AVGs model were applied in the groups of WT ND,WT HFD,and CHOP KO HFD.Human umbilical vein endothelial cells(HUVECs)were cultured with oxidized low density lipoprotein(ox-LDL)(40 mg/L)for the indicated time lengths(0,6,12,24 h).ERS inhibitor tauroursodeoxycholic acid(TUDCA)was used to block ERS.Immunohistochemical staining was used to observe the changes of ICAM1.Changes of ERS were detected by real-time RT-PCR.Protein expression levels and ERS activation were detected by Western blotting.Endothellial cell function was determined by endothelial permeability assay and transendothelial migration assay.Results HFD increased neointima formation in AVGs associated with endothelial dysfunction.At the same time,ERS was increased in endothelial cells(ECs)after AVGs in mice consuming the HFD.In vitro,ox-LDL was found to stimulate ERS,increase the permeability of the EC monolayer,and cause endothelial dysfunction.Blocking ERS with TUDCA or CHOP siRNA reversed the EC dysfunction caused by ox-LDL.In vivo,knockout of CHOP(CHOP KO)protected the function of ECs and decreased neointima formation after AVGs in HFD mice.Conclusion Inhibiting ERS in ECs could improve the function of AVGs.展开更多
文摘Optical coherence tomography （OCT） is a new imaging modality with resolution of approximately 10 pm and can be employed to visualize intracoronary characteristics. Sirolimus-eluting stents （SES） are susceptible to late thrombosis due to delayed reendothelialization over the stent struts, which may result in acute myocardial infarction or death. This study was designed to evaluate the re-endothelialization and neointimal coverage of SES with OCT 6 months and 12 months after implantation.Methods A total of 36 patients enrolled in the study underwent OCT examination 6 months （17 patients） and 12 months （19 patients） after SES implantation, The strut apposition to the vessel wall and neointimal coverage on SES struts were evaluated by OCT, Results Forty-six SES and 6561 struts were analyzed, At 6 months, 3041 struts （98.7%） were well-apposed and 39 struts （1,3%） were malapposed, At 12 months, 3434 struts （98,6%） were well-apposed and 47 struts （1,4%） were malapposed, Furthermore, only 4 SES at 6 months （18,2%） and 10 SES at 12 months （41,7%） were fully covered by neointimal growth, The average neointimal thicknesses covering the analyzed struts at 6 months and 12 months were （42±28） μm and （88±32） μm, respectively, There were 1989 struts at 6 months （72,1%） and 1461 struts at 12 months （45,6%） with neointimal thickness 〈100 μm, Conclusions OCT was able to visualize the strut apposition to the vessel wall and neointimal coverage on SES struts, At 6-month and 12-month follow-up examinations most struts were covered with thin neointima, but few of the entire SES showed full coverage. To prevent late-stent thrombosis in the presence of uncovered stent struts, longer dual antiplatelet drugs therapy should be recommended,
基金The study was supported by a grant from Beijing Municipal Nature Science Fund (No. 7042021).
文摘Percutaneous coronary intervention （PCI） with drug-eluting stent implantation has been provedefficient to reduce complications and restenosis in type B2/C lesions compared with bare stent, since the major drawback of the latter technique is intimal hyperplasia from the vessel media, which significantly cause in-stent restonosis. Despite the beneficial effects on the renin-angiotensin-aldosterone （RAAS） system, the role of angiotensin-converting enzyme （ACE） inhibitors after PCI is still unclear. However, first results of angiotensin receptor antagonist （valsartan） after stent implantation in the VaI-PREST1 and VALVACE2 trials have indicated the systemic pharmacological effect in the prevention of in-stent-restenosis. Up to our knowledge, whether local treatment of valsartan by implanting drug-eluting stent can generally prevent restenosis by inhibiting intimal hyperplasia has not been explored.
文摘目的应用光学相干断层成像（OCT）技术比较冠状动脉内雷帕霉素药物洗脱支架（DES）和金属裸支架（BMS）治疗后内膜增殖情况.方法对19例冠心病经冠状动脉内支架置入治疗后5～93个月的患者进行冠状动脉造影复查,造影后对21支血管23个支架进行OCT成像检查.DES术后6～10个月为药物支架A组;BMS术后5～10个月为金属裸支架B组;BMS术后23～93个月为金属裸支架C组.应用OCT成像技术比较3组支架之间内膜增殖情况.结果 OCT成像结果显示3组之间有关支架后最大内膜增殖厚度、血管腔直径和截面积丢失及直径和截面积再狭窄等方面差异有统计学意义.其中A组内膜最大增殖厚度明显小于B组（0.20 mm±0.13 mm vs 0.81 mm±0.46 mm,P=0.019）和C组（0.91 mm±0.27 mm,P=0.007）; A组血管腔直径丢失明显小于B组（0.27 mm ±0.17 mm vs 1.12 mm±0.79 mm,P=0.009）和C组（1.20 mm±0.31 mm P=0.013）;A组直径再狭窄明显小于B组（8%±4% vs 36%±24%, P=0.009）和C组（35%±6%,P=0.017）;A组截面积丢失明显小于B组（1.14 mm2 ±0.9 mm2 vs 3.96 mm2±2.62 mm,P=0.009）和C组（4.66 mm2±1.66 mm2,P=0.006）;A组截面积再狭窄明显小于B组（P=0.017）和C组（P=0.009）.置入的13个BMS支架,几乎所有支架支撑杆表面均有内膜覆盖,而置入DES后内膜增殖较少,部分支架支撑杆表面即使在支架术后29个月仍然没有内膜覆盖.结论 OCT成像技术可清晰地显示支架支撑杆及表面内膜增殖情况,对评价药物洗脱支架的治疗效果具有重要意义.
文摘Background： Endothelial cell damage is an important pathophysiological step of restenosis after angioplasty and stenting. Cell transplantation has great therapeutic potential for endothelial recovery. We investigated the effect of transplanting endothelial progenitor cells （EPCs） derived from human early fetal aortas in rat injured arteries. Methods： The carotid arterial endothelium of Sprague-Dawley rats was damaged by dilatation with a 1.5 F balloon catheter, and then EPCs derived from human early fetal aortas （〈14 weeks） were injected into the lumen of the injured artery in transplanted rats, with an equal volume of normal saline injected into control rats. Rats were sacrificed at 2 and 4 weeks after treatment and transplanted cells were identified by immunohistochemical staining with anti-human CD31 and anti-human mitochondria antibodies. Arterial cross-sections were analyzed by pathology, immunohistochemistry, and morphometry. Results： Green fluorescence-labeled EPCs could be seen in the endovascular surface of balloon-injured vessels after transplantation. The intimal area and intimal/medial area ratio were significantly smaller in the transplanted group than in the control （P 〈 0.05） and the residual lumen area was larger （P 〈 0.05）. After EPC transplantation, a complete vascular endothelial layer was formed, which was positive for human yon Willebrand factor after immunohistochemical staining, and immunohistochemical staining revealed many CD31- and mitochondria-positive cells in the re-endothelialized endothelium with EPC transplantation but not control treatment. Conclusion： EPCs derived from human early fetal aorta were successfully transplanted into injured vessels and might inhibit neointimal hyperplasia after vascular injury.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 30770899 to NIE Ru-qiong）, the Natural Science Foundation of Guangdong Province （No. 8151008901000072 to NIE Ru-qiong）.
文摘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.
基金Supported by Funds from NYMC Research Endowment Fund under the College’s intramural support program(RM)the National Institutes of Health(JEL,R01 HL111259)K23 HL098743(EDA)
文摘AIM: To study the genesis of neointima formation in pulmonary hypertension(PH), we investigated the role of caveolin-1 and related proteins. METHODS: Male Sprague Dawley rats were given monocrotaline(M, 40 mg/kg) or subjected to hypobaric hypoxia(H) to induce PH. Another group was given M and subjected to H to accelerate the disease process(M + H). Right ventricular systolic pressure, right ventricular hypertrophy, lung histology for medial hypertrophy and the presence of neointimal lesions were examined at 2 and 4 wk. The expression of caveolin-1 and its regulatory protein peroxisome proliferator-activated receptor(PPAR) γ, caveolin-2, proliferative and antiapoptotic factors(PY-STAT3, p-Erk, Bcl-x L), endothelial nitric oxide synthase(e NOS) and heat shock protein(HSP) 90 in the lungs were analyzed, and the results from M + H group were compared with the controls, M and H groups. Double immunofluorescence technique was used to identify the localization of caveolin-1 in pulmonary arteries in rat lungs and in human PH lung tissue. RESULTS: In the M + H group, PH was more severe compared with M or H group. In the 4 wk M+H group, several arteries with reduced caveolin-1 expression in endothelial layer coupled with an increased expression in smooth muscle cells(SMC), exhibited neointimal lesions. Neointima was present only in the arteries exhibiting enhanced caveolin-1 expression in SMC. Lung tissue obtained from patients with PH also revealed neointimal lesions only in the arteries exhibiting endothelial caveolin-1 loss accompanied by an increased caveolin-1 expression in SMC. Reduction in e NOS and HSP90 expression was present in the M groups(2 and 4 wk), but not in the M + H groups. In both M groups and in the M + H group at 2 wk, endothelial caveolin-1 loss was accompanied by an increase in PPARγ expression. In the M + H group at 4 wk, increase in caveolin-1 expression was accompanied by a reduction in the PPARγ expression. In the H group, there was neither a loss of endothelial caveolin-1, eNOS or HSP 90, nor
基金funded by the National Natural Science Foundation of China(No.81770413)Hubei Provincial Natural Science Foundation of China(No.2017CFB669).
文摘Objective Endothelial dysfunction is one candidate for triggering neointima formation after arteriovenous grafts(AVGs),but the factors mediating this process are unclear.The purpose of this study was to investigate the role of endoplasmic reticulum stress(ERS)-induced endothelial dysfunction in neointima formation following AVGs in high-fat diet(HFD)mice.Methods CCAAT-enhancer-binding protein-homologous protein(CHOP)knockout(KO)mice were created.Mice were fed with HFD to produce HFD model.AVGs model were applied in the groups of WT ND,WT HFD,and CHOP KO HFD.Human umbilical vein endothelial cells(HUVECs)were cultured with oxidized low density lipoprotein(ox-LDL)(40 mg/L)for the indicated time lengths(0,6,12,24 h).ERS inhibitor tauroursodeoxycholic acid(TUDCA)was used to block ERS.Immunohistochemical staining was used to observe the changes of ICAM1.Changes of ERS were detected by real-time RT-PCR.Protein expression levels and ERS activation were detected by Western blotting.Endothellial cell function was determined by endothelial permeability assay and transendothelial migration assay.Results HFD increased neointima formation in AVGs associated with endothelial dysfunction.At the same time,ERS was increased in endothelial cells(ECs)after AVGs in mice consuming the HFD.In vitro,ox-LDL was found to stimulate ERS,increase the permeability of the EC monolayer,and cause endothelial dysfunction.Blocking ERS with TUDCA or CHOP siRNA reversed the EC dysfunction caused by ox-LDL.In vivo,knockout of CHOP(CHOP KO)protected the function of ECs and decreased neointima formation after AVGs in HFD mice.Conclusion Inhibiting ERS in ECs could improve the function of AVGs.
