RESUMO
Objective The expression level of monocyte chemoattractant protein-1 (MCP-1) is increased in atherosclerotic regions, inducing monocyte migration to the blood vessel wall. Although the serum MCP-1 concentration is higher in patients with than without cardiovascular disease, the precise correlations between the serum MCP-1 concentration and factors associated with smoking and atherosclerosis are unknown. Methods The serum MCP-1 concentration was measured using an enzyme-linked immunosorbent assay in 207 consecutive smokers who visited our smoking cessation clinic. Results Sex-adjusted analysis of smokers revealed that the MCP-1 concentration was positively correlated with age ( ß = 0.311), smoking duration ( ß = 0.342), systolic blood pressure ( ß = 0.225), and diastolic blood pressure ( ß = 0.137) but not with the body mass index. Multivariate regression analysis showed that smoking duration and systolic blood pressure were independent determinants of the MCP-1 concentration. Conclusions The MCP-1 concentration was positively correlated with blood pressure among smokers. Long-term smokers with high blood pressure may be more susceptible to plaque rupture at atherosclerotic lesion sites.
Assuntos
Pressão Sanguínea , Quimiocina CCL2/sangue , Fumar Cigarros/sangue , Hipertensão/diagnóstico , Abandono do Hábito de Fumar , Idoso , Biomarcadores/sangue , Determinação da Pressão Arterial , Índice de Massa Corporal , Fumar Cigarros/fisiopatologia , Feminino , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Protein related to DAN and cerberus (PRDC) is a secreted protein characterized by a cysteine knot structure, which binds bone morphogenetic proteins (BMPs) and thereby inhibits their binding to BMP receptors. As an extracellular BMP antagonist, PRDC may play critical roles in osteogenesis; however, its expression and function in osteoblastic differentiation have not been determined. Here, we investigated whether PRDC is expressed in osteoblasts and whether it regulates osteogenesis in vitro. PRDC mRNA was found to be expressed in the pre-osteoblasts of embryonic day 18.5 (E18.5) mouse calvariae. PRDC mRNA expression was elevated by treatment with BMP-2 in osteoblastic cells isolated from E18.5 calvariae (pOB cells). Forced expression of PRDC using adenovirus did not affect cell numbers, whereas it suppressed exogenous BMP activity and endogenous levels of phosphorylated Smad1/5/8 protein. Furthermore, PRDC inhibited the expression of bone marker genes and bone-like mineralized matrix deposition in pOB cells. In contrast, the reduction of PRDC expression by siRNA elevated alkaline phosphatase activity, increased endogenous levels of phosphorylated Smad1/5/8 protein, and promoted bone-like mineralized matrix deposition in pOB cells. These results suggest that PRDC expression in osteoblasts suppresses differentiation and that reduction of PRDC expression promotes osteogenesis in vitro. PRDC is accordingly identified as a potential novel therapeutic target for the regulation of bone formation.