RESUMO
OBJECTIVES: The biological functions of transforming growth factor-ß signaling that involves Smad proteins have not been previously investigated with respect to coronary artery bypass grafts. The aim of the present study was to observe the immunostaining of proteins that are related to this signaling pathway. METHODS: Fifteen remnants of coronary artery bypass grafts, including nine saphenous veins, three radial arteries and three mammary arteries, were collected from 12 patients who were undergoing coronary artery bypass. Hematoxylin and eosin, Masson's trichrome, and immunohistochemical staining of transforming growth factor-ß1, type I receptor of transforming growth factor-ß, Smad2/3, Smad4, and Smad7 were performed. RESULTS: The saphenous veins showed more severe intimal degeneration, more severe smooth muscle cell proliferation and more collagen deposition than the arterial grafts, as evidenced by hematoxylin and eosin and Masson's trichrome stainings. Immunohistochemical assays demonstrated that the majority of the transforming growth factor-ß1 signaling cytokines were primarily localized in the cytoplasm in the medial layers of all three types of grafts, whereas ectopic transforming growth factor-ß1, type I receptor of transforming growth factor-ß, and Smad7 overexpressions in the interstices were observed particularly in the saphenous vein and radial arterial grafts. CONCLUSION: Enhanced transforming growth factor-ß1 signal transduction with medial smooth muscle cell proliferation and ectopic transforming growth factor-ß1, the presence of the type I receptor of transforming growth factor-ß, and Smad7 overexpressions in the extracellular matrix may provide primary evidence for early or late graft failure.
Assuntos
Artéria Torácica Interna/química , Disfunção Primária do Enxerto/metabolismo , Artéria Radial/química , Veia Safena/química , Fator de Crescimento Transformador beta/análise , Idoso , Idoso de 80 Anos ou mais , Ponte de Artéria Coronária , Feminino , Humanos , Imuno-Histoquímica , Masculino , Artéria Torácica Interna/patologia , Pessoa de Meia-Idade , Músculo Liso Vascular/química , Músculo Liso Vascular/patologia , Disfunção Primária do Enxerto/patologia , Artéria Radial/patologia , Veia Safena/patologia , Transdução de SinaisRESUMO
OBJECTIVES: The biological functions of transforming growth factor-β signaling that involves Smad proteins have not been previously investigated with respect to coronary artery bypass grafts. The aim of the present study was to observe the immunostaining of proteins that are related to this signaling pathway. METHODS: Fifteen remnants of coronary artery bypass grafts, including nine saphenous veins, three radial arteries and three mammary arteries, were collected from 12 patients who were undergoing coronary artery bypass. Hematoxylin and eosin, Masson's trichrome, and immunohistochemical staining of transforming growth factor-β1, type I receptor of transforming growth factor-β, Smad2/3, Smad4, and Smad7 were performed. RESULTS: The saphenous veins showed more severe intimal degeneration, more severe smooth muscle cell proliferation and more collagen deposition than the arterial grafts, as evidenced by hematoxylin and eosin and Masson's trichrome stainings. Immunohistochemical assays demonstrated that the majority of the transforming growth factor-β1 signaling cytokines were primarily localized in the cytoplasm in the medial layers of all three types of grafts, whereas ectopic transforming growth factor-β1, type I receptor of transforming growth factor-β, and Smad7 overexpressions in the interstices were observed particularly in the saphenous vein and radial arterial grafts. CONCLUSION: Enhanced transforming growth factor-β1 signal transduction with medial smooth muscle cell proliferation and ectopic transforming growth factor-β1, the presence of the type I receptor of transforming growth factor-β, and Smad7 overexpressions in the extracellular matrix may provide primary evidence for early or late graft failure.
Assuntos
Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Torácica Interna/química , Disfunção Primária do Enxerto/metabolismo , Artéria Radial/química , Veia Safena/química , Fator de Crescimento Transformador beta/análise , Ponte de Artéria Coronária , Imuno-Histoquímica , Artéria Torácica Interna/patologia , Músculo Liso Vascular/química , Músculo Liso Vascular/patologia , Disfunção Primária do Enxerto/patologia , Artéria Radial/patologia , Transdução de Sinais , Veia Safena/patologiaRESUMO
Transmural electrical stimulation of the sympathetic nerve endings of human saphenous vein biopsies released two forms of NPY identified chromatographically as native and oxidized peptide. The release process is dependent on extracellular calcium, the frequency, and the duration of the stimuli. While guanethidine reduced the overflow of ir-NPY, phenoxybenzamine did not augment NPY release, but increased that of noradrenaline. Oxidized NPY, like native NPY, potentiated the noradrenaline and adenosine 5'-triphospahate-induced vasoconstriction, an effect blocked by BIBP 3226 and consonant with the RT-PCR detection of the mRNA encoding the NPY Y1 receptor. These results highlight the functional role of NPY in human vascular sympathetic reflexes.
Assuntos
Neuropeptídeo Y/fisiologia , Veia Safena/inervação , Trifosfato de Adenosina/farmacologia , Idoso , Cálcio/metabolismo , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Estimulação Elétrica , Guanetidina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuropeptídeo Y/metabolismo , Fenoxibenzamina/farmacologia , Veia Safena/química , Veia Safena/efeitos dos fármacos , Transmissão Sináptica , VasoconstriçãoRESUMO
BACKGROUND: It is known that the sympathetic varicosities co-store and co-release norepinephrine (NE) together with adenosine S-triphosphate (ATP) and neuropeptide Y (NPY). AIM: To describe the chemical characterization of stored and released NPY from the varicosities of sympathetic nerve terminals surrounding segments of the human saphenous vein, and the vasomotor activity of rings electrically depolarized or contracted by the exogenous application of the co-transmitters. MATERIAL AND METHODS: Saphenous vein tissues were obtained from patients undergoing elective cardiac revascularization surgery. RESULTS: The chromatographic profile of NPY extracted from biopsies is identical to a chemical standard of human NPY. Upon electrical depolarisation of the perivascular sympathetic nerve terminals, we demonstrated the release of NPY to the superfusion media, which did not exceed a 1% of its stored content. The release of the peptide is sensitive to guanethidine, and to extracellular calcium, suggesting that the mechanism of its release is exocytotic in nature. The electrically evoked release of NPY is dependent on the frequency and duration of the electrical pulses. Phenoxybenzamine reduces the electrically evoked release of NPY. Exogenous application of NE and ATP contract saphenous vein rings; the simultaneous application of NE plus ATP causes a synergic response, effect which is further potentiated by the joint co-application of 10 nM NPY. CONCLUSIONS: Present results highlight the role of NPY as a sympathetic co-transmitter in the regulation of human vascular tone.
Assuntos
Trifosfato de Adenosina/farmacologia , Neuropeptídeo Y/fisiologia , Veia Safena/inervação , Transmissão Sináptica/fisiologia , Estimulação Elétrica , Humanos , Neuropeptídeo Y/análise , Neuropeptídeo Y/farmacologia , Neurotransmissores/farmacologia , Norepinefrina/farmacologia , Sistema Nervoso Periférico/efeitos dos fármacos , Veia Safena/química , Veia Safena/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Resistência VascularRESUMO
Se usó un sistema in vitro para medir la producción de PG12 en anillos aislados de la arteria mamaria interna, la arteria epigástrica inferior y la vena safena obtenidos en 5 pacientes durante cirugía de revascularización. La muestras fueron incubadas en solución Krebs'Ringer a pH 7.4. Por radioinmuoensayo (Amersham) se midió el 6-keto-PGF la, metabolito de PG12 en alicuotas del sobrenadante. La producción de arterias epigástrica fue 12,5 2,0 ng/mg/30 min, la de arteria mamaria interna 9,3 1,7 y la de vena safena5,1 0,7 (p 0,01). Por lo tanto, la arteria epigástrica inferior produce PG12 en cantidades similares a las de la arteria mamaria interna y considerablemente mayores que las de la vena safena. Ello podría traducirse en un mejor pronóstico de los puentes coronarios efectuados con arteria epigástrica comparados con las de la vena safena