Objective: To examine the expression and localisation of adrenomedullln in hum an coronary atherosclerotic lesions from patients with unstable angina(UAP) and stable angina(SAP), and to study the relation between adre...Objective: To examine the expression and localisation of adrenomedullln in hum an coronary atherosclerotic lesions from patients with unstable angina(UAP) and stable angina(SAP), and to study the relation between adrenomedullin expression and plaque instability. Design: A retrospective observational study. Patients: D irectional coronary atherectomy samples were obtained from 15 patients with UAP and 12 with SAP. Methods: The localisation of adrenomedullin was examined by imm unohistochemistry, and adrenomedullin mRNA expression was measured by quantitati ve polymerase chain reaction. Results: Adrenomedullin immunoreactivity was prefe rentially localised in macrophages, intimai smooth muscle cells, and proliferate d microvessels. The mean number of adrenomedullin positive cells in five high po wer fields(x 400) per specimen was higher in patients with UAP than in those wit h SAP (mean (SEM), 110(13) v 76 (7); p< 0.05); and the ratio of adrenomedullin p ositive to total cells was higher in patients with UAP (43.0 (2.2)%v 34.2 (2.0) %; p< 0.01). More adrenomedullin mRNA was expressed in the plaque of patients w ith UAP than in those with SAP (60.4 (16.9)%v 9.7 (3.3)%; p< 0.01). Conclusion s: The findings suggest that adrenomedullin is involved in the development of at herosclerosis and plaque instability in human coronary arteries, in an autocrine or paracrine manner.展开更多
Objective: To design an extravascular trestle model coated phosphorus-32, an isotope radiating beta rays, and investigate its effects on intimal hyperplasia of autologous vein grafts. Methods: ETA cDNA was used as a g...Objective: To design an extravascular trestle model coated phosphorus-32, an isotope radiating beta rays, and investigate its effects on intimal hyperplasia of autologous vein grafts. Methods: ETA cDNA was used as a gene probe specific to vascular SMCs on the basis of in situ hybridization. The femoral veins were transplanted reversely into colateral femoral arteries in rabbits, and the animals were divided into control, chemical agents and phosphorus-32 groups. The morphometry was applied to calculate the ETA cDNA expression and intimal thickness. Spearman correlation method was utilized to investigate their relationship. Results: Intimal thickness in grafts of phosphorus-32 group was markedly reduced. Additionally, intimal ETA gene expression was also decreased in beta rays group. The values increased at a slower rate significantly different from that of control and aspirin groups (P<0.01). The correlation of ETA cDNA expression and intimal thickness exhibited a strongly positive relation. Conclusion: Beta rays in extravascular model could remarkably inhibit intimal thickening and SMC proliferation. The correlation is an indirect evidence indicating that intimal hyperplasia composed of SMCs proliferation. It suggests that ETA cDNA expression could be a quantitative estimation of vascular SMC because of its specifics.展开更多
Objective:To determine the effects of a recombinant replication-deficient adenovirus encoding human tissue inhibitor of metalloproteinase-4(Ad.TIMP-4) on vascular smooth muscle cell(VSMC) function in vitro and neointi...Objective:To determine the effects of a recombinant replication-deficient adenovirus encoding human tissue inhibitor of metalloproteinase-4(Ad.TIMP-4) on vascular smooth muscle cell(VSMC) function in vitro and neointimal development in the injured rat carotid artery.Methods:Western blotting,gelatin zymography and reverse zymography were used to characterize the expression and functional activity of the TIMP-4 secreted by Ad.TIMP-4-infected VSMCs.The migration and proliferation of VSMCs in vitro were separately detected by using Millicell-PCF invasion chambers and [3H]-thymidine incorporation assay.Immunohistochemistry and morphometric analysis were used to determine the local expression of TIMP-4 and its effect on neointima development in a rat carotid artery balloon injury model.Results:VSMCs infected with Ad.TIMP-4 expressed functionally active human TIMP-4 which increased with the duration of infection.TIMP-4 expression inhibited VSMC migration,but not significantly affect VSMC proliferation.In a balloon-injured rat carotid artery model,a significant 62% reduction in neointimal area was found in Ad.TIMP-4-infected vessels at 14 days after injury.Ad.TIMP-4 infection had no effect on medial area.Conclusion:Our results indicated TIMP-4 over expression can significantly inhibit the migration of cultured VSMCs and prevent neointimal formation after vascular injury.Our findings provide additional evidence that TIMP-4 could play an important role in vascular pathophysiology,and may be an important therapeutic target for future drug development.展开更多
文摘Objective: To examine the expression and localisation of adrenomedullln in hum an coronary atherosclerotic lesions from patients with unstable angina(UAP) and stable angina(SAP), and to study the relation between adrenomedullin expression and plaque instability. Design: A retrospective observational study. Patients: D irectional coronary atherectomy samples were obtained from 15 patients with UAP and 12 with SAP. Methods: The localisation of adrenomedullin was examined by imm unohistochemistry, and adrenomedullin mRNA expression was measured by quantitati ve polymerase chain reaction. Results: Adrenomedullin immunoreactivity was prefe rentially localised in macrophages, intimai smooth muscle cells, and proliferate d microvessels. The mean number of adrenomedullin positive cells in five high po wer fields(x 400) per specimen was higher in patients with UAP than in those wit h SAP (mean (SEM), 110(13) v 76 (7); p< 0.05); and the ratio of adrenomedullin p ositive to total cells was higher in patients with UAP (43.0 (2.2)%v 34.2 (2.0) %; p< 0.01). More adrenomedullin mRNA was expressed in the plaque of patients w ith UAP than in those with SAP (60.4 (16.9)%v 9.7 (3.3)%; p< 0.01). Conclusion s: The findings suggest that adrenomedullin is involved in the development of at herosclerosis and plaque instability in human coronary arteries, in an autocrine or paracrine manner.
文摘Objective: To design an extravascular trestle model coated phosphorus-32, an isotope radiating beta rays, and investigate its effects on intimal hyperplasia of autologous vein grafts. Methods: ETA cDNA was used as a gene probe specific to vascular SMCs on the basis of in situ hybridization. The femoral veins were transplanted reversely into colateral femoral arteries in rabbits, and the animals were divided into control, chemical agents and phosphorus-32 groups. The morphometry was applied to calculate the ETA cDNA expression and intimal thickness. Spearman correlation method was utilized to investigate their relationship. Results: Intimal thickness in grafts of phosphorus-32 group was markedly reduced. Additionally, intimal ETA gene expression was also decreased in beta rays group. The values increased at a slower rate significantly different from that of control and aspirin groups (P<0.01). The correlation of ETA cDNA expression and intimal thickness exhibited a strongly positive relation. Conclusion: Beta rays in extravascular model could remarkably inhibit intimal thickening and SMC proliferation. The correlation is an indirect evidence indicating that intimal hyperplasia composed of SMCs proliferation. It suggests that ETA cDNA expression could be a quantitative estimation of vascular SMC because of its specifics.
基金Supported by the National Natural Science Foundation of China (30630056)
文摘Objective:To determine the effects of a recombinant replication-deficient adenovirus encoding human tissue inhibitor of metalloproteinase-4(Ad.TIMP-4) on vascular smooth muscle cell(VSMC) function in vitro and neointimal development in the injured rat carotid artery.Methods:Western blotting,gelatin zymography and reverse zymography were used to characterize the expression and functional activity of the TIMP-4 secreted by Ad.TIMP-4-infected VSMCs.The migration and proliferation of VSMCs in vitro were separately detected by using Millicell-PCF invasion chambers and [3H]-thymidine incorporation assay.Immunohistochemistry and morphometric analysis were used to determine the local expression of TIMP-4 and its effect on neointima development in a rat carotid artery balloon injury model.Results:VSMCs infected with Ad.TIMP-4 expressed functionally active human TIMP-4 which increased with the duration of infection.TIMP-4 expression inhibited VSMC migration,but not significantly affect VSMC proliferation.In a balloon-injured rat carotid artery model,a significant 62% reduction in neointimal area was found in Ad.TIMP-4-infected vessels at 14 days after injury.Ad.TIMP-4 infection had no effect on medial area.Conclusion:Our results indicated TIMP-4 over expression can significantly inhibit the migration of cultured VSMCs and prevent neointimal formation after vascular injury.Our findings provide additional evidence that TIMP-4 could play an important role in vascular pathophysiology,and may be an important therapeutic target for future drug development.
