RESUMO
AbstractObjective:Matrix metalloproteinases are inflammatory biomarkers involved in carotid plaque instability. Our objective was to analyze the inflammatory activity of plasma and carotid plaque MMP-8 and MMP-9 after intravenous administration of hydrocortisone.Methods:The study included 22 patients with stenosis ≥ 70% in the carotid artery (11 symptomatic and 11 asymptomatic) who underwent carotid endarterectomy. The patients were divided into two groups: Control Group - hydrocortisone was not administered, and Group 1 - 500 mg intravenous hydrocortisone was administered during anesthetic induction. Plasma levels of MMP-8 and MMP-9 were measured preoperatively (24 hours before carotid endarterectomy) and at 1 hour, 6 hours and 24 hours after carotid endarterectomy. In carotid plaque, tissue levels of MMP-8 and MMP-9 were measured.Results:Group 1 showed increased serum levels of MMP- 8 (994.28 pg/ml and 408.54 pg/ml, respectively; P=0.045) and MMP-9 (106,656.34 and 42,807.69 respectively; P=0.014) at 1 hour after carotid endarterectomy compared to the control group. Symptomatic patients in Group 1 exhibited lower tissue concentration of MMP-8 in comparison to the control group (143.89 pg/ml and 1317.36 respectively; P=0.003). There was a correlation between preoperative MMP-9 levels and tissue concentrations of MMP-8 (P=0.042) and MMP-9 (P=0.019) between symptomatic patients in the control group.Conclusion:Hydrocortisone reduces the concentration of MMP- 8 in carotid plaque, especially in symptomatic patients. There was an association between systemic and tissue inflammation.
ResumoObjetivo:As metaloproteinases são biomarcadores inflamatórios envolvidos na instabilidade da placa carotídea. O objetivo deste estudo foi analisar a atividade inflamatória da MMP-8 e MMP-9 plasmática e presente na placa carotídea, após administração intravenosa de hidrocortisona.Métodos:Participaram do estudo 22 pacientes portadores de estenose ≥ 70% em artéria carótida (11 sintomáticos e 11 assintomáticos), submetidos à endarterectomia de artéria carótida. Os pacientes foram divididos em dois grupos: Grupo Controle - não foi administrado hidrocortisona e Grupo 1 - foi administrado 500 mg intravenoso de hidrocortisona durante a indução anestésica. As dosagens plasmáticas de MMP-8 e MMP-9 foram efetuadas no pré-operatório (24 horas antes da endarterectomia de artéria carótida) e em 1 hora, 6 horas e 24 horas após endarterectomia de artéria carótida. Na placa carotídea foram mensurados os níveis teciduais de MMP-8 e MMP-9.Resultados:O grupo 1 exibiu elevação dos níveis séricos da MMP-8 (994,28 pg/ml e 408,54 pg/ml, respectivamente; P=0.045) e MMP-9 (106.656,34 e 42.807,69, respectivamente; P=0.014) em 1 hora após a endarterectomia de artéria carótida, em relação ao grupo controle. Os pacientes sintomáticos do grupo 1 exibiram menor concentração tecidual de MMP-8, em relação ao grupo controle (143,89 pg/ml e 1317,36, respectivamente; P=0.003). Houve correlação entre os níveis pré-operatórios de MMP-9 e as concentrações teciduais de MMP-8 (P=0.042) e MMP-9 (P=0.019) entre os pacientes sintomáticos do grupo controle.Conclusão:A hidrocortisona reduz a concentração de MMP-8 na placa carotídea, em especial nos pacientes sintomáticos. Houve associação entre a inflamação sistêmica e a tecidual.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/farmacologia , Artéria Carótida Interna/efeitos dos fármacos , Estenose das Carótidas/cirurgia , Hidrocortisona/farmacologia , /efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Biomarcadores/análise , Artéria Carótida Interna/enzimologia , Estenose das Carótidas/enzimologia , Endarterectomia das Carótidas , Hidrocortisona/uso terapêutico , /análise , Metaloproteinase 9 da Matriz/análise , Período Pós-Operatório , Valores de Referência , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Matrix metalloproteinases are inflammatory biomarkers involved in carotid plaque instability. Our objective was to analyze the inflammatory activity of plasma and carotid plaque MMP-8 and MMP-9 after intravenous administration of hydrocortisone. METHODS: The study included 22 patients with stenosis ≥ 70% in the carotid artery (11 symptomatic and 11 asymptomatic) who underwent carotid endarterectomy. The patients were divided into two groups: Control Group - hydrocortisone was not administered, and Group 1 - 500 mg intravenous hydrocortisone was administered during anesthetic induction. Plasma levels of MMP-8 and MMP-9 were measured preoperatively (24 hours before carotid endarterectomy) and at 1 hour, 6 hours and 24 hours after carotid endarterectomy. In carotid plaque, tissue levels of MMP-8 and MMP-9 were measured. RESULTS: Group 1 showed increased serum levels of MMP- 8 (994.28 pg/ml and 408.54 pg/ml, respectively; P=0.045) and MMP-9 (106,656.34 and 42,807.69 respectively; P=0.014) at 1 hour after carotid endarterectomy compared to the control group. Symptomatic patients in Group 1 exhibited lower tissue concentration of MMP-8 in comparison to the control group (143.89 pg/ml and 1317.36 respectively; P=0.003). There was a correlation between preoperative MMP-9 levels and tissue concentrations of MMP-8 (P=0.042) and MMP-9 (P=0.019) between symptomatic patients in the control group. CONCLUSION: Hydrocortisone reduces the concentration of MMP- 8 in carotid plaque, especially in symptomatic patients. There was an association between systemic and tissue inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Artéria Carótida Interna/efeitos dos fármacos , Estenose das Carótidas/cirurgia , Hidrocortisona/farmacologia , Metaloproteinase 8 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Biomarcadores/análise , Artéria Carótida Interna/enzimologia , Estenose das Carótidas/enzimologia , Endarterectomia das Carótidas , Feminino , Humanos , Hidrocortisona/uso terapêutico , Masculino , Metaloproteinase 8 da Matriz/análise , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Período Pós-Operatório , Valores de Referência , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do TratamentoRESUMO
Progesterone and 17ß-estradiol induce vasorelaxation through non-genomic mechanisms in several isolated blood vessels; however, no study has systematically evaluated the mechanisms involved in the relaxation induced by 17ß-estradiol and progesterone in the canine basilar and internal carotid arteries that play a key role in cerebral circulation. Thus, relaxant effects of progesterone and 17ß-estradiol on KCl- and/or PGF2α-pre-contracted arterial rings were investigated in absence or presence of several antagonists/inhibitors/blockers; the effect on the contractile responses to CaCl2 was also determined. In both arteries progesterone (5.6-180 µM) and 17ß-estradiol (1.8-180 µM): (1) produced concentration-dependent relaxations of KCl- or PGF2α-pre-contracted arterial rings; (2) the relaxations were unaffected by actinomycin D (10 µM), cycloheximide (10 µM), SQ 22,536 (100 µM) or ODQ (30 µM), potassium channel blockers and ICI 182,780 (only for 17ß-estradiol). In the basilar artery the vasorelaxation induced by 17ß-estradiol was slightly blocked by tetraethylammonium (10mM) and glibenclamide (KATP; 10 µM). In both arteries, progesterone (10-100 µM), 17ß-estradiol (3.1-31 µM) and nifedipine (0.01-1 µM) produced a concentration-dependent blockade of the contraction to CaCl2 (10 µM-10mM). These results suggest that progesterone and 17ß-estradiol produced relaxation in the basilar and internal carotid arteries by blockade of L-type voltage dependent Ca(2+) channel but not by genomic mechanisms or production of cAMP/cGMP. Potassium channels did not play a role in the relaxation to progesterone in both arteries or in the effect of 17ß-estradiol in the internal carotid artery; meanwhile KATP channels play a minor role on the effect of 17ß-estradiol in the basilar artery.
Assuntos
Canais de Cálcio/metabolismo , Estradiol/administração & dosagem , Progesterona/administração & dosagem , Vasodilatação/efeitos dos fármacos , Animais , Artéria Basilar/efeitos dos fármacos , Artéria Basilar/fisiologia , Artéria Carótida Interna/efeitos dos fármacos , Artéria Carótida Interna/fisiologia , Humanos , Técnicas de Cultura de Órgãos , Canais de Potássio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vasodilatação/fisiologiaRESUMO
AIM: To compare the effect of conjugated estrogen (CEE) versus conjugated estrogen and medroxyprogesterone acetate (MPA) therapy on internal carotid artery pulsatility index (PI) in postmenopausal women. MATERIAL & METHODS: In the prospective, randomized, single-blinded comparative study, postmenopausal women meeting the inclusion criteria were randomized into one of two groups: CEE group (CEE 0.625 mg/day), or CEE + MPA group (CEE 0.625 mg/day plus MPA 2.5 mg/day). Patients were submitted to blood tests (total cholesterol, high-density lipoprotein cholesterol, triglycerides and total glucose) and to color Doppler ultrasound of the internal carotid artery to assess PI at the beginning of the study. Ultrasound was repeated after 16 weeks of treatment. Statistical analysis was performed using Student's t-test or two-way analysis of variance for repeated measures. Data were considered to be significant at P < 0.05. RESULTS: Seventy-five postmenopausal women (age 53.3 ± 5.5 years) were included in the study. There was a statistically significant reduction in PI in both groups after 16 weeks of hormonal treatment. However, there was no difference between the two groups (group 1: 0.8960 to 0.8450; group 2: 0.9048 to 0.8426). CONCLUSION: The use of CEE and CEE associated with MPA during 16 weeks led to an improvement in internal carotid flow as measured by PI, with no difference between the treatments.
Assuntos
Doenças das Artérias Carótidas/prevenção & controle , Artéria Carótida Interna/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/uso terapêutico , Acetato de Medroxiprogesterona/uso terapêutico , Pós-Menopausa , Fluxo Pulsátil/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Método Simples-CegoRESUMO
This study assessed the effect of 3 lipid-lowering therapies on the reduction of the carotid intima-media thickness (IMT) in high-risk coronary Mexican patients. The study was a randomized, comparative, and open clinical trial. Ninety high-risk coronary patients were allocated to 3 groups: pravastatin 40 mg, simvastatin 40 mg, and simvastatin 20 mg and ezetimibe 10 mg initially. If the therapeutic goals were not attained (<100 mg/dL of low-density lipoprotein cholesterol [LDL-C] for type C and <70 mg for type D), patients in group 1 received pravastatin 40 mg and ezetimibe 10 mg, group 2 received simvastatin 80 mg, and group 3 received simvastatin 40 mg and ezetimibe 10 mg. The primary endpoint was the change of IMT over the course of 1 year. The secondary endpoints were changes in LDL-C and in high sensitive C-reactive protein (CRPhs). The overall baseline IMTs generated by combining measurements in the internal carotid artery were 1.33+/-0.32 mm, 1.30+/-0.11 mm, and 1.23+/-0.28 mm for groups 1, 2, and 3, respectively. After 1 year, IMT values were 0.93+/-0.13 mm, 0.90+/-0.11 mm, and 0.92+/-0.01 mm for groups 1, 2, and 3, respectively. At the end of the study, LDL-C levels were 48+/-41, 45+/-37, and 48+/-31 in groups 1, 2, and 3, respectively. No significant differences were observed in CRP, high-density lipoprotein cholesterol, triglycerides, blood pressure, and body mass index, among the groups. This study is one of the first providing evidence that dual therapy has a beneficial effect on a surrogate marker of atherosclerosis.