RESUMO
Marfan syndrome, a connective tissue disorder affecting the cardiovascular system, is caused by mutations of fibrillin-based microfibrils. These mutations often affect the calcium-binding domains, resulting in structural changes to the proteins. It is hypothesized that these Ca+2 binding sites regulate the structure and mechanical properties of the microfibrils. The mechanical properties of fresh and extracted lobster aortic rings in calcium solutions (1, 13 and 30 mM Ca+2) were measured. Samples underwent amino acid compositional analysis. Antibodies were produced against the material comprising extracted aortic rings. The ultrastructure of strained and unstrained samples was examined using transmission electron microscopy. Calcium level altered the tangent modulus of fresh vessels. These rings were significantly stiffer when tested at 30 mM Ca+2 compared to rings tested at 1 mM Ca+2. Amino acid comparisons between extracted samples, porcine and human fibrillin showed compositional similarity. Immunohistochemical analysis showed that antibodies produced against the material in extracted samples localized to the known microfibrillar elements in the lobster aorta and cross-reacted with fibrillin microfibrils of mammalian ciliary zonules. Ultrastructurally, vessels incubated in low calcium solutions showed diffuse interbead regions while those incubated in physiological or high calcium solutions showed interbead regions with more defined lateral edges.
Assuntos
Aorta Abdominal/fisiologia , Microfibrilas/metabolismo , Microfibrilas/ultraestrutura , Nephropidae/fisiologia , Aminoácidos/análise , Animais , Aorta Abdominal/química , Aorta Abdominal/ultraestrutura , Fenômenos Biomecânicos , Cálcio/metabolismo , Reações Cruzadas , Elasticidade , Fibrilinas , Técnicas In Vitro , Mamíferos/imunologia , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/imunologia , Microscopia Eletrônica de Transmissão , Relaxamento Muscular , ViscosidadeRESUMO
Calcium appears to be involved in many of the cellular events which are thought to be important in atherogenesis. Calcium channel blockers have been shown to reduce arterial lipid accumulation in animals without altering serum cholesterol. Avian models of atherosclerosis offer economic and technical advantages over mammalian models. In this study, we examine the effects of nifedipine, verapamil and diltiazem at clinical and higher doses, on the extent of atherosclerosis of egg-fed chickens. In order to assess the extent of atherosclerosis quantitatively, the aortic lesions of the thoracic and abdominal aorta, aortic arch and supraaortic regions were measured by planimetry. Atherosclerotic lesions were evaluated histologically. Statistically significant reductions in the lipid deposition of the aorta were found in all the treated groups. The extent and distribution of atherosclerotic lesions were decreased in a significant way by verapamil, nifedipine and diltiazem. The higher the dosage used, the higher the regression of the atherosclerotic lesions. At clinical dosage, nifedipine showed the highest decrease of the lesions. In addition, the chicken atherosclerosis model has proved itself useful and very suitable for in vivo drug intervention studies.
Assuntos
Aorta Abdominal/patologia , Aorta Torácica/patologia , Arteriosclerose/tratamento farmacológico , Arteriosclerose/patologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Galinhas/fisiologia , Diltiazem/uso terapêutico , Nifedipino/uso terapêutico , Verapamil/uso terapêutico , Animais , Aorta Abdominal/ultraestrutura , Aorta Torácica/ultraestrutura , Colesterol na Dieta/farmacologia , Corantes , Dieta Aterogênica , Masculino , Microscopia Eletrônica , Fixação de TecidosRESUMO
Growth factor and extracellular matrix gene expression by vessel wall cells influence the development of arterial lesions. In this study, we compared the level of acidic and basic fibroblast growth factor mRNA expression in aortic vessels from normal swine and from swine with dietary-induced vascular lesions. There was a striking increase in the level of acidic fibroblast growth factor mRNA within the lesions while the level of basic fibroblast growth factor mRNA decreased. Swine fed an atherosclerotic diet supplemented with L-arginine developed atherosclerotic plaques that also contained increased levels of acidic fibroblast growth factor mRNA. We also examined the expression level of a number of extracellular matrix and cytoskeletal mRNAs to compare the biosynthetic state of normal arteries and atherosclerotic plaques. Compared with the normal artery, the level of alpha-smooth muscle actin mRNA decreased, and there was a concomitant increase in vimentin, fibronectin and thrombospondin mRNA levels. Surprisingly, alpha 1(I), alpha 2(I) and alpha 1(III) collagen mRNA levels were decreased in the atherosclerotic lesions when compared with the normal artery. These results indicate that vascular lesion formation in hypercholesterolemic swine is accompanied by alterations in growth factor, cytoskeletal and extracellular matrix gene expression.
Assuntos
Arteriosclerose/metabolismo , Citoesqueleto/metabolismo , Dieta Aterogênica , Fator 1 de Crescimento de Fibroblastos/genética , RNA Mensageiro/metabolismo , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/ultraestrutura , Arginina/administração & dosagem , Arteriosclerose/etiologia , Arteriosclerose/patologia , Sequência de Bases , Colágeno/genética , Matriz Extracelular , Fator 2 de Crescimento de Fibroblastos/genética , Fibronectinas/genética , Glicoproteínas de Membrana/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Suínos , Trombospondinas , Vimentina/genéticaRESUMO
The descending thoracic and abdominal aortas of normal and hypercholesterolemic Golden Syrian hamsters were examined with transmission electron microscopy and immunofluorescence microscopy. Serum cholesterol distribution in lipoproteins was determined by gradient ultracentrifugation. Luminal surfaces appeared free of lesions and no intimal thickening or foam cells were seen. The main rise of cholesterol during the hypercholesterolemic diet was in the VLDL + IDL fraction. These findings suggest differences in the localization of atherosclerotic lesions and lipoprotein cholesterol distribution between humans and hamsters, which hamper the use of this species as a model for human atherosclerosis.