RESUMEN
Although mineral deposits have long been described to be a prominent feature of atherosclerosis, the mechanisms of arterial calcification are not well understood. However, accumulation of the non-collagenous matrix bone-associated proteins, osteopontin, osteocalcin, and osteonectin, has been demonstrated in atheromatous plaques. The aim of this study was to evaluate the role of these proteins in arterial calcification and, more precisely, during the initiation of this process. A model of rapid aortic calcification was developed in rabbits by an oversized balloon angioplasty. Calcification was followed using von Kossa staining and osteopontin, osteocalcin, and osteonectin were identified using immunohistochemistry. The aortic injury was rapidly followed by calcified deposits that appeared in the media as soon as 2 days after injury and then accumulated in zipper-like structures. Osteonectin was not detected in calcified deposits at any time after injury. In contrast, osteopontin and osteocalcin were detected in 8- and 14-day calcified structures, respectively, but not in the very early 2-day mineral deposits. These results suggest that these matrix proteins, osteopontin, osteocalcin, and osteonectin, are not involved in the initiation step of the aortic calcification process and that the former two might play a role in the regulation of arterial calcification.
Asunto(s)
Arteriosclerosis/metabolismo , Calcinosis/metabolismo , Osteocalcina/metabolismo , Osteonectina/metabolismo , Sialoglicoproteínas/metabolismo , Túnica Media/metabolismo , Angioplastia de Balón/efectos adversos , Animales , Aorta/metabolismo , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/metabolismo , Calcinosis/etiología , Inmunohistoquímica , Masculino , Microscopía Confocal , Osteopontina , ConejosRESUMEN
Increased large artery stiffness is believed to be a cardiovascular risk factor independent from mean arterial pressure. The mechanical properties of large arteries depend not only on the amounts of their main constituents (elastin, collagen, and smooth muscle cells) but also on the spatial organization and mechanical interactions among these components. These interactions may be mediated by extracellular matrix adhesion proteins and their membrane receptors or integrins. From a mechanical viewpoint, a key element may be the dense plaque, which is composed of cytoskeletal proteins linked to matrix proteins via membrane integrin receptors. Integrin expression in normal and diseased blood vessels is currently the focus of active research. In humans, hypertension-related arterial hypertrophy is not associated with an increase in intrinsic arterial wall stiffness. Aortic fibronectin expression is increased in spontaneously hypertensive rats (SHRs). By increasing cell-matrix anchoring, fibronectin may contribute to protect arterial wall components from the increased mechanical loads associated with hypertension. In atherosclerosis, the increase in cell-matrix anchoring plays a key role in preventing atheroma plaque rupture. To determine the exact role of adhesion molecules in arterial stiffness, there is a need for studies involving use of specific anti-integrin agents and of transgenic animal models.
Asunto(s)
Arterias/fisiopatología , Enfermedades Cardiovasculares/fisiopatología , Matriz Extracelular/patología , Animales , Arterias/patología , Enfermedades Cardiovasculares/patología , Humanos , Factores de RiesgoRESUMEN
There is a paucity of studies in the literature concerning the structural characteristics of the arterial wall in the abdominal region using human material and specialized morphometric techniques. In the present study we carry out the morphometric study, describing a series of structural peculiarities in 12 segments of the human splenic artery. Among these the presence of length-wise or spiral-shaped muscular columns in the medial layer which mark and reduce the diameter of the arterial lumen is of major importance. In its underlying intima small localized thickenings appear which, with age may become generalized. We also analyze the different intimal thickenings and such indices as the Intimal Thickening Index, Lumen Reduction Index and Pathologic Thickening Index, with differences among the groups we have considered. The study of elastin in the various parietal structures help us to understand the possible pathogenesis of the thickenings, and to clarify the important morphological-functional correlation for the regulation of blood flow which exists in this arterial region.
Asunto(s)
Músculo Liso Vascular/anatomía & histología , Arteria Esplénica/anatomía & histología , Adolescente , Adulto , Biometría , Tejido Elástico/anatomía & histología , Humanos , Persona de Mediana Edad , Arteria Esplénica/crecimiento & desarrolloRESUMEN
Smooth muscle cell proliferation is an important feature of atherogenesis. Some works have hypothesized that a transformation of smooth muscle cells could arise during this pathological process. The present paper describes two spontaneously transformed cell lines of arterial smooth muscle cells (SMC) established from aortic media of adult rat. The cell lines have been designated V6 and V8; some of their morphologic, growth, and metabolic characteristics are described and compared to their parent cells. The two cell lines appeared distinct by their morphology and by their degree of transformation. V6 cells appeared as elongated spindle-shaped cells whereas V8 cells were spread cells with a cobblestone pattern. Karyotypes of both cell lines showed a high polyploidy level. V6 and V8 cell lines were immortalized and showed growth characteristics of transformed cells: low requirement of serum to grow, ability to form colonies in soft agar and tumorigenicity in nude mice; V8 cells presented a higher malignancy than V6 cells. Both V6 and V8 cells exhibited characteristics of cultured arterial SMC: ultrastructure, alpha actin expression at the protein and mRNA level, prostacyclin production. The remarkably different morphologies of the V6 and V8 lines and their transformed phenotype suggest that these cell lines could be useful models to study SMC differentiation and proliferation with respect to atherosclerotic or hypertensive vascular diseases.
Asunto(s)
Transformación Celular Neoplásica/patología , Músculo Liso Vascular/citología , Actinas/genética , Actinas/metabolismo , Animales , Aorta/citología , Ácidos Araquidónicos/metabolismo , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Línea Celular Transformada , Epoprostenol/metabolismo , Citometría de Flujo , Cariotipificación , Masculino , Ratones , Ratones Desnudos , Microscopía Electrónica , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/ultraestructura , Ploidias , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas EndogámicasRESUMEN
The influence of transcortin and of cortisol on RNA synthesis in thymus chromatin, have been tested. The experimental results show that cortisol alone has no effect on RNA synthesis. But, in the same conditions of ionic strength, a serious decrease in transcription, induced by cortisol-transcortin complex, is demonstrated.