RESUMO
Until recently, 3,5-diiodothyronine (3,5-T(2)) has been considered an inactive by-product of triiodothyronine (T(3)) deiodination. However, studies from several laboratories have shown that 3,5-T(2) has specific, nongenomic effects on mitochondrial oxidative capacity and respiration rate that are distinct from those due to T(3). Nevertheless, little is known about the putative genomic effects of 3,5-T(2). We have previously shown that hyperthyroidism induced by supraphysiological doses of 3,5-T(2) inhibits hepatic iodothyronine deiodinase type 2 (D2) activity and lowers mRNA levels in the killifish in the same manner as T(3) and T(4), suggesting a pretranslational effect of 3,5-T(2) (Garcia-G C, Jeziorski MC, Valverde-R C, Orozco A. Gen Comp Endocrinol 135: 201-209, 2004). The question remains as to whether 3,5-T(2) would have effects under conditions similar to those that are physiological for T(3). To this end, intact killifish were rendered hypothyroid by administering methimazole. Groups of hypothyroid animals simultaneously received 30 nM of either T(3), reverse T(3), or 3,5-T(2). Under these conditions, we expected that, if it were bioactive, 3,5-T(2) would mimic T(3) and thus reverse the compensatory upregulation of D2 and tyroid receptor beta1 and downregulation of growth hormone that characterize hypothyroidism. Our results demonstrate that 3,5-T(2) is indeed bioactive, reversing both hepatic D2 and growth hormone responses during a hypothyroidal state. Furthermore, we observed that 3,5-T(2) and T(3) recruit two distinct populations of transcription factors to typical palindromic and DR4 thyroid hormone response elements. Taken together, these results add further evidence to support the notion that 3,5-T(2) is a bioactive iodothyronine.
Assuntos
Di-Iodotironinas/farmacologia , Fundulidae/fisiologia , Hormônio do Crescimento/sangue , Iodeto Peroxidase/metabolismo , Glândula Tireoide/fisiologia , Receptores beta dos Hormônios Tireóideos/metabolismo , Animais , Di-Iodotironinas/sangue , Regulação Enzimológica da Expressão Gênica/fisiologia , Hipertireoidismo/metabolismo , Hipertireoidismo/fisiopatologia , Hipotireoidismo/metabolismo , Hipotireoidismo/fisiopatologia , Iodeto Peroxidase/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Elementos de Resposta/fisiologia , Glândula Tireoide/efeitos dos fármacos , Regulação para Cima/fisiologia , Iodotironina Desiodinase Tipo IIRESUMO
This report compares quantitative measures of atherosclerosis in aortas and coronaries from autopsies of deceased men from Mexico City collected during 1960 to 1964 and 1986 to 1987. The comparison of lesions in two different time periods provides an opportunity for determining whether the extent of atherosclerosis has changed over time in Mexico City. Three pathologists independently evaluated the extent of fatty streaks (FS), fibrous plaques (FP), calcified plaques (CA), and complicated lesions (CO) in 165 aortas and 120 sets of coronary arteries collected during 1986 to 1987 for comparison with similar gradings of 128 aortas and coronary arteries from the International Atherosclerosis Project in 1960 to 1964. Neither FS nor more advanced lesions differed significantly in either the descending thoracic or abdominal aorta between the two collection periods. In contrast, there were more extensive FP and raised atherosclerotic lesions (RL = FP + CA + CO) in the coronary artery segments evaluated in the younger age groups in 1986 to 1987 versus 1960 to 1964. Additional analyses, based on 75 pairs of aortas and 32 pairs of coronary arteries from age-matched cases, all regraded by the team of pathologists after blind coding, showed more FS in both aortic segments and more extensive involvement with RL in the three main branches of the coronary arteries in the more recent study. An overview of our findings suggests that atherosclerosis, particularly in the coronary arteries, is increasing in Mexico City. This hypothesis merits careful testing in parallel with consideration of possible changes in the risk factors that could be responsible for changes in extent of lesions.
Assuntos
Arteriosclerose/epidemiologia , Adolescente , Adulto , Fatores Etários , Aorta Abdominal/patologia , Aorta Torácica/patologia , Arteriosclerose/patologia , Vasos Coronários/patologia , Humanos , Masculino , México , Pessoa de Meia-Idade , Distribuição Aleatória , Estudos RetrospectivosRESUMO
Topographic and morphologic aspects of coronary atherosclerotic "protruding" lesions were investigated in 119 accidental deaths in males living in Mexico City. Morphology and topography varied according to the arterial trunk studied and age. Left anterior descending and circumflex lesions were almost always confined to the initial 5 cms and if a lesion was present after the 3rd cm there was always a proximal lesion. Right coronary lesions occasionally were found distally even in the absence of proximal lesions. Third decade lesions were usually not calcified. Stenosis if present was rarely multivascular. Some fourth decade lesions were calcified; plurivascular stenosis was present in some cases. Fifth decade lesions show sequential stenotic lesions in the same vessel; calcium and plurivascular stenosis were often observed. However the features observed in the 3rd decade could be observed in the older subjects. Reference is made to lesions which are found in both the left main trunk and the left anterior descending. Epidemiological and clinical applications related with preventive programs are mentioned.