ABSTRACT
Ethnicity is an important determinant of blood pressure levels, being black individuals affected more than any other ethnic group. Arterial stiffening, an independent risk factor for hypertension, is also influenced by ethnicity. However, whether black individuals from different continents would have different patterns of arterial stiffening is still unknown. Thus, the authors aimed to compare pulse wave velocity (PWV) in black subjects living in Angola and Brazil. A total of 677 black individuals from two independent cross-sectional studies conducted in Brazil and Angola were included in this analysis. Carotid-to-femoral PWV was measured following the same protocols for both studies, as well as clinical and anthropometric variables. Adjusted PWV was higher in Brazilian blacks than in Angolans, regardless of sex (men from Brazil: 10.7 ± 1.8 vs men from Angola: 9.9 ± 1.8 m/s, P < .001; women from Brazil: 10.3 ± 1.5 vs women from Angola: 9.2 ± 1.3 m/s, P < .001). Although the cf-PWV was higher in Brazilian blacks, the age-related increase in cf-PWV was higher in Angolan men compared to Brazilians, but not in women. SBP showed the strongest association with cf-PWV, regardless of sex and country. However, age was associated with cf-PWV in all groups, except in Brazilian men. Our results clearly show a difference in PWV between two black populations, and highlight for sex differences in the hemodynamic parameters that might affect blood pressure levels in these populations.
Subject(s)
Hypertension , Vascular Stiffness , Adult , Black or African American , Angola/epidemiology , Blood Pressure , Brazil/epidemiology , Cross-Sectional Studies , Female , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Male , Pulse Wave AnalysisABSTRACT
Usurpation of the host's signalling pathways is a common strategy employed by viruses to promote their successful replication. Here we show that infection with the orthopoxvirus vaccinia virus (VACV) leads to sustained stimulation of c-Jun activity during the entire infective cycle. This stimulation is temporally regulated through MEK/ERK or MKK/JNK pathways, i.e. during the early/mid phase (1 to 6 hpi) and in the late phase (9 to 24 hpi) of the infective cycle, respectively. As a transcriptional regulator, upon infection with VACV, c-Jun is translocated from the cytoplasm to the nucleus, where it binds to the AP-1 DNA sequence found at the promoter region of its target genes. To investigate the role played by c-Jun during VACV replication cycle, we generated cell lines that stably express a c-Jun-dominant negative (DNc-Jun) mutation. Our data revealed that c-Jun is required during early infection to assist with viral DNA replication, as demonstrated by the decreased amount of viral DNA found in the DNc-Jun cells. We also demonstrated that c-Jun regulates the expression of the early growth response gene (egr-1), a gene previously shown to affect VACV replication mediated by MEK/ERK signalling. VACV-induced stimulation of the MKK/JNK/JUN pathway impacts viral dissemination, as we observed a significant reduction in both viral yield, during late stages of infection, and virus plaque size. Collectively, our data suggest that, by modulating the host's signalling pathways through a common target such as c-Jun, VACV temporally regulates its infective cycle in order to successfully replicate and subsequently spread.
Subject(s)
Extracellular Signal-Regulated MAP Kinases/metabolism , MAP Kinase Kinase 4/metabolism , MAP Kinase Kinase Kinases/metabolism , Mitogen-Activated Protein Kinase Kinases/metabolism , Proto-Oncogene Proteins c-jun/metabolism , Vaccinia virus/physiology , Animals , Cell Line , DNA, Viral , Early Growth Response Protein 1/genetics , Early Growth Response Protein 1/metabolism , Extracellular Signal-Regulated MAP Kinases/genetics , Fibroblasts/virology , Gene Expression Regulation, Enzymologic/physiology , Gene Expression Regulation, Viral/physiology , MAP Kinase Kinase 4/genetics , MAP Kinase Kinase Kinases/genetics , Mice , Mitogen-Activated Protein Kinase Kinases/genetics , Phosphorylation , Proto-Oncogene Proteins c-jun/genetics , Virus ReplicationABSTRACT
The pharmacological inhibitor SP600125 [anthra(1,9-cd)pyrazol-6(2H)-one 1,9-pyrazoloanthrone] has been largely employed as a c-JUN N-terminal kinase (JNK1/2) inhibitor. In this study, we evaluated whether pretreatment with SP600125 was able to prevent Orthopoxviruses Vaccinia virus (VACV), Cowpox virus (CPXV) and modified Vaccinia virus Ankara (MVA) replication. We found that incubation with SP600125 not only blocked virus-stimulated JNK phosphorylation, but also, significantly reduced virus production. We observed 1-3 log decline in viral yield depending on the cell line infected (A31, BSC-40 or BHK-21). The reduction in viral yield correlated with a dramatic impact on virus morphogenesis progress, intracellular mature viruses (IMV) were barely detected. Despite the fact that SP600125 can act as an efficient anti-orthopoxviral compound, we also provide evidence that this antiviral effect is not specifically exerted through JNK1/2 inhibition. This conclusion is supported by the fact that viral titers measured after infections of JNK1/2 knockout cells were not altered as compared to those of wild-type cells. In contrast, a decline in viral titers was verified when the infection of KO cells was carried out in the presence of the pharmacological inhibitor. SP600125 has been the focus of recent studies that have evaluated its action on diverse viral infections including DNA viruses. Our data support the notion that SP600125 can be regarded as a potential antipoxviral compound.
