ABSTRACT
Mechanisms that control the balance between cell proliferation and death are important in the development of vascular lesions. Rat primary smooth muscle cells were 80% inhibited by low microgram doses of hydrocortisone (HC) and 50% inhibited by nanogram concentrations of transforming growth factor-beta1 (TGF-beta1), although some lines acquired resistance in late passage. However, comparable doses of HC, or TGF-beta1, failed to inhibit most human lesion-derived cell (LDC) lines. In sensitive LDC, HC (10 microg/mL) inhibited proliferation by up to 50%, with obvious apoptosis in some lines, and TGF-beta1 inhibited proliferation by more than 90%. Collagen production, as measured by [3H]proline incorporation or RIA for type III pro-collagen, was either unaffected or increased in the LDCs by HC. These divergent responses between LDC lines were partially explained by the absence of the glucocorticoid receptor (GR) and heat shock protein 90 mRNA in 10 of 12 LDC lines, but the presence of the mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type II. Western blot analysis confirmed the absence of the GR protein in cells lacking GR mRNA. Immunohistochemistry of human carotid lesions showed high levels of GR in the tunica media, but large areas lacking GR in the fibrous lesion. Considering the absence of the GR in most lines, the effects of HC may be elicited through the mineralocorticoid receptor. Functional resistance to the antiproliferative and antifibrotic effects of HC may contribute to excessive wound repair in atherosclerosis and restenosis.
Subject(s)
Arteriosclerosis/pathology , Down-Regulation , Hydrocortisone/pharmacology , Muscle, Smooth, Vascular/drug effects , Receptors, Glucocorticoid/deficiency , Transforming Growth Factor beta/pharmacology , 11-beta-Hydroxysteroid Dehydrogenases , Animals , Apoptosis/drug effects , Arteriosclerosis/metabolism , Arteriosclerosis/surgery , Carotid Arteries/pathology , Carotid Arteries/surgery , Carotid Artery Injuries , Cell Division/drug effects , Cells, Cultured , DNA Replication/drug effects , Drug Resistance , Endarterectomy , Enzyme Induction , Femoral Artery/injuries , Femoral Artery/pathology , Femoral Artery/surgery , HSP70 Heat-Shock Proteins/biosynthesis , HSP90 Heat-Shock Proteins/biosynthesis , HSP90 Heat-Shock Proteins/deficiency , HSP90 Heat-Shock Proteins/genetics , Humans , Hydroxysteroid Dehydrogenases/analysis , Iliac Artery/injuries , Iliac Artery/pathology , Iliac Artery/surgery , Male , Muscle, Smooth, Vascular/metabolism , Procollagen/biosynthesis , Procollagen/genetics , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , RNA, Messenger/analysis , Rats , Rats, Inbred F344 , Receptors, Glucocorticoid/biosynthesis , Receptors, Glucocorticoid/genetics , Receptors, Mineralocorticoid/analysis , Recurrence , Species SpecificityABSTRACT
A study was undertaken on 1,474 school children of either sex, aged six to 12, from the community of Toluca, Mexico State, selected by dual-stage conglomerate sampling, both from rural and urban areas. Data registered included teeth with caries, lost teeth and filled cavities for permanent dentition, and teeth with caries, extracted or obturated teeth in the case of primary dentition. Periodontal health status was evaluated according to World Health Organization criteria, and conditions of occlusion were graded according to Angle's classification.
