RESUMEN
Vascular pathology is characterized by important alterations of some vessel macromolecular constituents, such as fibrous proteins, collagens and elastin. The purpose of our study was to establish the activity of benzquercin treatment on such alterations of the vascular wall. As experimental model we used lathyrism induced in mice by chronic administration of beta-amino-propionitril (beta-APN). This compound prevents crosslink-formation in elastin and collagen and provokes a disorganization of the structure and an alteration of the physiological functions of the vascular wall. The connective tissue of the skin is also impaired simultaneously with that of the blood vessels. We compared by optical and transmission electron microscopy the morphological structure of the aorta and the skin of 3 groups of mice: a normal control group, an other which only received the beta-APN alone and a third one which received the beta-APN and the benzquercin treatment. The second group, injected with beta-APN without treatment, showed important alterations of the structure of the aorta as well as of the skin. Both fibrous proteins, collagen and elastin were concerned by these alterations, the consequence of which was an increase of the permeability of the aorta wall demonstrated with the horse-radish peroxydase as a tracer. The third group, injected with beta-APN and treated with the benzquercin, showed much less morphological disorders than the untreated group and the vascular permeability was also close to normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Aminopropionitrilo/farmacología , Aorta Torácica/efectos de los fármacos , Permeabilidad Capilar/efectos de los fármacos , Tejido Conectivo/efectos de los fármacos , Flavonoides/farmacología , Aminopropionitrilo/efectos adversos , Animales , Aorta Torácica/ultraestructura , Colágeno/análisis , Tejido Conectivo/ultraestructura , Combinación de Medicamentos , Tejido Elástico/efectos de los fármacos , Tejido Elástico/ultraestructura , Latirismo/inducido químicamente , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Valores de Referencia , Piel/efectos de los fármacos , Piel/ultraestructuraRESUMEN
Varicose vein walls differ from normal venous walls by an important loss of their collagen content and an increase of their glycosaminoglycan content, essentially of hyaluronan. The decrease in fibrous protein content can be attributed to increased proteolytic (collagenolytic) activity as well as to free radicals. Glycosaminoglycan increase reflects a disregulation of the normal program of matrix biosynthesis by the cells of varicose vein wall, essentially smooth muscle cells. Some flavonoid drugs are capable of correcting these deviations by decreasing proteolytic attack on fibrous proteins and the accumulation of proteoglycans and hyaluronan. These effects, due to interactions between flavonoid drugs and the cells and fibrous proteins of the venous wall differ according to the nature of such drugs. A hypothesis is proposed to explain these differences in the intensity of action of flavonoid drugs with apparently closely related structures, based on the conformation of these drugs and their interaction with the triple helical structure of collagen fibers as well as with the cell membranes.
Asunto(s)
Biflavonoides , Matriz Extracelular/metabolismo , Flavonoides/uso terapéutico , Glicosaminoglicanos/metabolismo , Músculo Liso Vascular/metabolismo , Proantocianidinas , Várices/metabolismo , Antihipertensivos/química , Antihipertensivos/uso terapéutico , Catequina/análogos & derivados , Catequina/química , Catequina/uso terapéutico , Matriz Extracelular/química , Femenino , Flavonoides/química , Glicosaminoglicanos/química , Humanos , Ácido Hialurónico/sangre , Ácido Hialurónico/química , Ácido Hialurónico/metabolismo , Masculino , Músculo Liso Vascular/química , Proteoglicanos/química , Proteoglicanos/metabolismo , Várices/sangre , Várices/tratamiento farmacológico , Várices/patologíaRESUMEN
We previously found that type V collagen repressed the attachment and spread of aortic smooth muscle cells. The present study was carried out to investigate the effects of type V collagen on the formation of fibronectin and F-actin filaments of human dermal fibroblasts in relation to cell attachment and spread, using an immunofluorescent technique and morphometry. The number and area of the cells attached to type V collagen at 1 and 3 hours after seeding were significantly lower than those of cells on other substrates, including collagen types I, III and IV, and bovine serum albumin. However, there was no significant difference in the attachment and spread among the cells on these substrates after 24 hours. Cultured fibroblasts exhibited two patterns of fibronectin; one was a clear, linear fibronectin localized mainly in the cellular margins, and the other was a granular or flocculent fibronectin found in the perinuclear areas. The former was stained in non-permeabilized cells, but not in trypsin-treated cells (cell surface fibronectin). In contrast, the latter was not detected in nonpermeabilized cells, but was found in trypsin-treated cells (perinuclear fibronectin). Most of the cells cultured on type V collagen did not form either linear cell surface fibronectin or F-actin filaments at 3 hours. In contrast, many cells on collagen types I, III, and IV developed both cell surface fibronectin and F-actin filaments, the distributions of which were partially coincident. Colocalization of linear cell surface fibronectin and F-actin filaments was found in cells on all of the substrates after 24 hours. Perinuclear fibronectin showed similar patterns, and was not colocalized with F-actin filaments on different substrates at 3 and 24 hours of culture. Solid-phase substrates induced a better cellular attachment at 3 hours than serum adhesive factors. The administration of monensin, which inhibits the secretion of protein products, decreased the intensity of the fluorescence of cell surface fibronectin in fibroblasts, which was observed in a clear line. These results suggest that the retardation of the initial attachment and spread of fibroblasts on type V collagen is related to an inhibition in the formation of the fibronexus, a close transmembranous association of individual fibronectin fibers and F-actin filaments.
Asunto(s)
Actinas/metabolismo , Colágeno/metabolismo , Fibroblastos/citología , Fibroblastos/metabolismo , Fibronectinas/metabolismo , Actinas/análisis , Adolescente , Adulto , Adhesión Celular/fisiología , Membrana Celular/metabolismo , Membrana Celular/fisiología , Membrana Celular/ultraestructura , Movimiento Celular/fisiología , Células Cultivadas , Niño , Colágeno/fisiología , Femenino , Fibroblastos/química , Fibroblastos/efectos de los fármacos , Fibronectinas/análisis , Fibronectinas/efectos de los fármacos , Técnica del Anticuerpo Fluorescente , Humanos , Monensina/farmacologíaRESUMEN
Effects of graded intensity exercise on plasma lipids was studied in Standardbred and Finnishbred Trotters. The rate of lipolysis indicated by the elevated plasma concentrations of glycerol increased parallel with the intensity of the trot in the Standardbreds, but not as clearly in the Finnishbred trotters. During the exercise plasma triglyceride concentration increased significantly and the increase correlated with the intensity of the exercise as well as the activity of lipolysis. Together with the increase in plasma triglycerides, there was a parallel increase in the pre-beta fraction of lipoproteins which suggests that the hepatic synthesis of triglycerides was increased. It was calculated that about one third of the nonesterified fatty acids released in lipolysis during the high-intensity exercise is oxidized and the remainder is used for resynthesis of triglycerides. Since there were interstrain differences in the concentrations of triglycerides and glycerol after the high-intensity exercise it is suggested that the differences may be of some value in the estimation of recovery after submaximal exercise.