RESUMO
AIM: To evaluate whether the presence of apical periodontitis (AP), root canal treatment (RCT) and endodontic burden (EB) - as the sum of AP and RCT sites - were associated with long-term risk of incident cardiovascular events (CVE), including cardiovascular-related mortality, using data on participants in the Baltimore Longitudinal Study of Ageing (BLSA). METHODOLOGY: This retrospective cohort included 278 dentate participants in the BLSA with complete medical and dental examinations. Periodontal disease (PD) and missing teeth were recorded. The total number of AP and RCT sites was determined from panoramic radiographs. EB was calculated as the sum of AP and RCT sites. Oral inflammatory burden (OIB) was calculated combining PD and EB. The main outcome was incident CVE including angina, myocardial infarction and cardiovascular-related death. Participants were monitored for up to 44 years (mean = 17.4± 11.1 years) following dental examination. Relative risks (RRs) were calculated through Poisson regression models, estimating the relationship between AP, RCT, EB, PD, OIB and incident CVE. RESULTS: Mean age at baseline was 55.0 ±16.8 years and 51.4% were men. Sixty-two participants (22.3%) developed CVE. Bivariate analysis showed that PD, EB, number of teeth and OIB were associated with incident CVE. Multivariate models, adjusted for socio-demographic and medical variables, showed that age ≥60 years (RR = 3.07, 95% CI =1.68-5.62), hypertension (RR = 2.0, 95% CI = 1.16-3.46) and EB ≥3 (RR = 1.77, 95% CI = 1.04-3.02) were independently associated with incident CVE. The association between OIB and incident CVE was reduced to nonsignificance after adjustments (RR = 1.97, 95% CI = 0.83-4.70). CONCLUSIONS: EB in midlife was an independent predictor of CVE amongst community-dwelling participants in the BLSA. Prospective studies are required to evaluate cardiovascular risk reduction with the treatment of AP.
Assuntos
Doenças Cardiovasculares/epidemiologia , Periodontite Periapical/epidemiologia , Periodontite Periapical/terapia , Tratamento do Canal Radicular , Baltimore , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Hereditary gingival fibromatosis (HGF) is a rare oral condition characterized by a slow and progressive enlargement of the gingiva, involving both the maxilla and mandible. In vitro, HGF fibroblasts demonstrate a proliferative index significantly higher than fibroblasts from normal gingiva (NG). The objective of this study was to determine the effect of dihydrotestosterone on the proliferation of gingival fibroblasts derived from patients with HGF (n = 4) and from four healthy individuals. Additionally, we analyzed the effect of dihydrotestosterone on interleukin-6 (IL-6) production and determined the expression levels of androgen receptors in NG and HGF fibroblasts. Gingival fibroblasts from NG and HGF were incubated with increasing concentrations of dihydrotestosterone with or without androgen blockers, and cultured for 24 h, and the proliferation index was determined by automated cell counter. IL-6 production, in this system, was quantified using a "capture" enzyme-linked immunosorbent assay (ELISA). Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to measure the mRNA expression of androgen receptors. The results indicated that dihydrotestosterone simultaneously downregulates the production of IL-6 and upregulates the cell proliferation. Finasteride and cyprosterone acetate, two anti-androgens, partially reversed these effects. Androgen receptor mRNA expression was identified in both NG and HGF fibroblasts; however, the levels in NG were higher than those observed in HGF. These results show that testosterone coordinates the proliferation and production of IL-6 of normal and HGF fibroblasts.
Assuntos
Fibroblastos/efeitos dos fármacos , Fibromatose Gengival/genética , Gengiva/efeitos dos fármacos , Interleucina-6/antagonistas & inibidores , Testosterona/farmacologia , Inibidores de 5-alfa Redutase , Adulto , Análise de Variância , Antagonistas de Androgênios/farmacologia , Contagem de Células , Técnicas de Cultura de Células , Divisão Celular/efeitos dos fármacos , Acetato de Ciproterona/farmacologia , Di-Hidrotestosterona/farmacologia , Regulação para Baixo , Inibidores Enzimáticos/farmacologia , Ensaio de Imunoadsorção Enzimática , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibromatose Gengival/metabolismo , Fibromatose Gengival/patologia , Finasterida/farmacologia , Gengiva/metabolismo , Gengiva/patologia , Humanos , Masculino , RNA Mensageiro/análise , Receptores Androgênicos/análise , Receptores Androgênicos/efeitos dos fármacos , Receptores Androgênicos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatística como Assunto , Testosterona/antagonistas & inibidores , Regulação para CimaRESUMO
Hereditary gingival fibromatosis (HGF) is characterized by an excess accumulation of extracellular matrix (ECM) resulting in a generalized and fibrotic enlargement of the gingiva. To investigate some of the regulatory features of this condition, gingival fibroblasts from normal gingiva (NG) and HGF were examined for the expression and production of matrix metalloproteinases (MMPs) and their inhibitors, tissue matrix metalloproteinases inhibitor (TIMPs). Our results, obtained from 2 different assays, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzymography, clearly demonstrated that the expression and production of MMP-1 and MMP-2 was significantly lower in fibroblasts from HGF than from NG. Interestingly, TIMP-1 and TIMP-2 expression from NG cells was shown to be slightly higher to those from HGF. Addition of antibodies against transforming growth factor-beta 1 (TGF-beta 1), which is produced in greater amounts by HGF fibroblasts, resulted in a slight increase in MMP-1 and a decrease in MMP-2 expression, whereas TIMP-1 and TIMP-2 expressions were unaffected. These patterns of expression and production suggest that enhanced TGF-beta 1 production reduce the proteolytic activities of HGF fibroblasts, which favor the accumulation of ECM.
Assuntos
Fibromatose Gengival/genética , Regulação Enzimológica da Expressão Gênica/fisiologia , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 2 da Matriz/genética , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-2/genética , Fator de Crescimento Transformador beta/biossíntese , Sequência de Bases , Células Cultivadas , Primers do DNA , Fibroblastos/enzimologia , Fibromatose Gengival/enzimologia , Gengiva/citologia , Gengiva/enzimologia , Humanos , Metaloproteinase 1 da Matriz/análise , Metaloproteinase 1 da Matriz/biossíntese , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/biossíntese , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Inibidor Tecidual de Metaloproteinase-2/análise , Inibidor Tecidual de Metaloproteinase-2/biossíntese , Fator de Crescimento Transformador beta/análiseRESUMO
HGF is a rare oral condition characterized by a slow, progressive enlargement of the gingiva, involving both the maxilla and mandible. HGF provides a model for the study of regulatory features of conditions characterized by connective tissue hyperplasia. In this study, the culture characteristics of gingival fibroblasts derived from patients of the same family with HGF (n = 4) were similar with regard to cell cycle analysis. Flow cytometric DNA content analysis revealed uniform DNA diploidy for fibroblasts cultured from NG and HGF. NG cells showed a low S-phase fraction (19.8%) and G2/M fraction (5.8%) and a relatively high G1 phase fraction (74%). In contrast, HGF cells from all members of the tested kindred, exhibited diploid cells with a higher S-phase (40.9%) and G2/M (10.1%) fraction and a relatively low G1 phase fraction (40.9%). Furthermore, we demonstrated that the expression and production of Hsp47 parallels the increased levels of collagen secretion observed in HGF. In addition, we show that Hsp47 and collagen are coordinately regulated following stress via a feedback mechanism mediated by N-terminal procollagen propeptides. Utilizing confocal microscopy and antibodies directed against GST-fusion proteins encompassing the pro alpha1(I) N-propeptide globular domain (NP1) (residues 23-108), it was apparent that this regulatory mechanism does not involve significant interaction with Hsp47's chaperoning of procollagen.