ABSTRACT
Introducción: La intervención coronaria percutánea (PCI en inglés) con implante de stent coronario es uno de los procedimientos más utilizados para la revascularización miocárdica en condiciones agudas o crónicas. Múltiples factores se han relacionado con la restenosis de stent, incluyendo aspectos clínicos, angiográficos, genéticos y epigenéticos. La respuesta inflamatoria en gran parte está determinada genéticamente y probablemente sea el rol más importante en la restenosis. El factor de necrosis tumoral a (TNF-α;) es un mediador clave en la respuesta inflamatoria actuando en sitios de injuria tisular inducida por el daño de las paredes del vaso. Objetivo: Determinar la asociación entre polimorfismos genéticos del TNF y restenosis en pacientes coronarios sometidos a angioplastía. Métodos: Se diseñó un estudio de casos y controles incidentes no pareados, aprobado por el comité de ética institucional. Se incluyeron pacientes con cardiopatía coronaria sometidos a PCI con implante de stent BMS o DES, con un tiempo de control angiográfico mayor de 6 meses. Los casos fueron definidos como aquellos pacientes con estenosis de stent >50% y como controles aquellos con estenosis <50%, con respecto del lumen del vaso de referencia. Se efectuó la genotipificación de los polimorfismos rs361525 (-238G/A) y rs1799964 (-1031 T/C) del gen TNF mediante PCR en tiempo real mediante sondas alelo-específicas. Además, se registraron variables clínicas y demográficas. Resultados: Se incluyó en este estudio de análisis de genotipificación del polimorfismo del gen TNF 82 pacientes como casos, y 102 controles. No hubo diferencias significativas en las siguientes variables clínicas y demográficas: edad (63.7 ± 10.5 vs. 65.4 ± 9.6 años; p=0.24), género masculino (75 vs. 69%, p=0.5), IMC (28.5 ± 3.6 vs. 28 ± 3.8 Kg/m2; p=0.78) y tabaquismo (79 vs. 77%; p=0.7). En contraste, se observó una diferencia significativa en la frecuencia de DM-2 casos y controles (43.2 vs. 26.5%; p=0.03) y %HbA1c entre ambos grupos (6.78 ± 1.5 vs. 6.1 ± 0.8%; p=0.01). Respecto a las variantes genéticas estudiadas, no hubo diferencias significativas en la frecuencia relativa del alelo mutado tanto para el polimorfismo rs361525 (Alelo A, casos: 0.06 vs. controles: 0.08; p=0.37), como para la variante rs1799964 (Alelo C, casos: 0.2 vs. controles: 0.2; p=0.96). Las OR asociadas a dichos alelos fueron 0.68 (I.C. 95%= 0.29 - 1.59) y 0.99 (I.C. 95%= 0.58 - 1.67), respectivamente; confirmando la ausencia de asociación. Conclusión: Nuestros datos sugieren que las variantes genéticas estudiadas no están relacionadas al desarrollo de restenosis en los sujetos estudiados, y probablemente en nuestra población los factores clínicos sean más determinantes para el desarrollo de reestenosis coronaria post angioplastía que los factores genéticos.
Multiple factors have been associated to the development of stent restenosis after coronary angioplasty (PCA). including clinical, angiographic, genetic and epigenetic factors. The inflammatory response is genetically determined and it may be the most important factor. Tumor necrosis factor a (TNFα) is a potent mediator of this response at the endothelial wall. Aim: To determine the association between TNFα; genetic polymorphisms and stent restenosis. Methods: A case-control study was performed in patients submitted to PTCA with stent implantation(-bare metal or drug eluting stent) at least 6 months prior to the study. Cases were defined by the presence of >50% intra stent stenosis. PCR was used for type classification of polymorphisms rs361525 (-238G/A) y rs1799964 (-1031 T/C) of the TNFα; gene. Results: 82 cases and 102 controls were included. No differences were observed in clinical and demographic variables: age (63.7 ± 10.5 vs. 65.4 ± 9.6 years, p=0.24, for cases and controls, respectively), male gender (75 vs. 69%, p=0.5), BMI (28.5 ± 3.6 vs. 28 ± 3.8 Kg/m2, p=0.78) and active smoking (79 vs. 77%, p=0.7). In contrast, Diabetes was more frequent in cases than in controls (43.2 vs. 26.5%, p=0.03). There was no difference in the relative frequency of mutations of the rs361525 polymorphism (Allele A, 0.06 vs 0.08, p=0.37 for cases and controls, respectively) nor for variant rs1799964 (0.2 in both cases and controls). Non significant associations were confirmed by Odd ratios with 0 included in the 95% confidence interval. Conclusion: No association of genetic polymorphisms of TNFa and stent restenosis was found, which suggests that clinical factors my be more important for the development of post PTCA stent restenosis.
Subject(s)
Humans , Male , Female , Polymorphism, Genetic/genetics , Tumor Necrosis Factor-alpha/genetics , Coronary Restenosis/genetics , Angioplasty, Balloon, Coronary , Case-Control Studies , Chi-Square Distribution , Stents/adverse effects , Coronary Restenosis/etiology , Real-Time Polymerase Chain Reaction , Genotype , Heart Diseases/therapyABSTRACT
BACKGROUND: Ruta graveolens L. (R. graveolens) is a medicinal plant employed in non-traditional medicines that has various therapeutic properties, including anthelmintic, and vasodilatory actions, among others. We evaluated the trachea-relaxant effects of hydroalcoholic extract of R. graveolens against potassium chloride (KCl)- and carbachol-induced contraction of rat tracheal rings in an isolated organ bath. RESULTS: The results showed that the airway smooth muscle contraction induced by the depolarizing agent (KCl) and cholinergic agonist (carbachol) was markedly reduced by R. graveolens in a concentration-dependent manner, with maximum values of 109 ± 7.9 % and 118 ± 2.6 %, respectively (changes in tension expressed as positive percentages of change in proportion to maximum contraction), at the concentration of 45 µg/mL (half-maximal inhibitory concentration IC50: 35.5 µg/mL and 27.8 µg/mL for KCl- and carbachol-induced contraction, respectively). Additionally, the presence of R. graveolens produced rightward parallel displacement of carbachol dose-response curves and reduced over 35 % of the maximum smooth muscle contraction. CONCLUSIONS: The hydroalcoholic extract of R. graveolens exhibited relaxant activity on rat tracheal rings. The results suggest that the trachea-relaxant effect is mediated by a non-competitive antagonistic mechanism. More detailed studies are needed to identify the target of the inhibition, and to determine more precisely the pharmacological mechanisms involved in the observed biological effects.