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Cyclophilin A is secreted by vascular smooth muscle cells in response to inflammatory stimuli, and could thus contribute to atherosclerosis. We hypothesized that the genetic variation at the cyclophilin A gene ( PPIA) could affect the risk for developing atherosclerosis and myocardial infarction. This study included 250 myocardial infarction patients (all male and < 60 years; 95% are smokers). All these cases had at least one atherosclerotic diseased coronary vessel. DNA was obtained from patients and from 250 healthy controls. The variation at the PPIA gene was determined in the patients through single-strand conformation analysis and direct sequencing of seven polymerase chain reaction fragments. Allele and genotype frequencies were compared between patients and controls. The effect of a promoter polymorphism (–11 G/C) on gene expression was in vitro analysed with luciferase-reporter assays. We found two common polymorphisms in the PPIA promoter (–11 G/C) and the 5′ non-translated (+36 G/A) regions. Cells transfected with luciferase-plasmids containing the –11 G had significantly higher luciferase activity. Genotype frequencies for these polymorphisms did not differ between patients and controls. In conclusion, we reported a functional variant in the PPIA promoter. However, the PPIA variation did not significantly contribute to the risk of suffering from myocardial infarction among patients with atherosclerotic diseased vessels. [ABSTRACT FROM AUTHOR]

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is one of the most common hereditary forms of stroke, and migraine with aura, mood disorders, or dementia, are also frequently found in these patients. Missense mutations in the Notch3 gene that create or destroy cysteine residues, have been found in most cases with a family history of the disease, although a few sporadic cases harbouring Notch3 mutations have also been described. Here, we describe a 44-year-old patient with clinical features of CADASIL who was a carrier of a new Notch3 mutation: cys128→gly. Both parents were alive and healthy, and negative for the mutation. This case illustrates the interest of analysing the Notch3 gene in cases with clinical features of CADASIL, even in the absence of a family history of the disease. [ABSTRACT FROM AUTHOR]

Neural crest cells are a dynamic migratory stem cell population that differentiates into a plethora of cell-types, including cells of the peripheral nervous system, endocrine cells, melanocytes, and cranio-facial bone and cartilage. In addition, neural crest cells are directly involved in various human health complications (tumors, heart valve malformations, cleft lip or palate). Despite their relevance little is known about the origin and induction of neural crest cells. (a) To analyze the participation of Wnt molecules during neural crest induction, and (b) to initiate studies of the earliest events in neural crest induction in gastrulating embryos. In vivo and in vitro inhibition and activation of Wnt and BMP signaling pathways, immunohistochemistry and RNA in situ hybridization. We have found that Wnt molecules are required and sufficient for neural crest cell induction. We also have found that unlike BMP4, a previously identified neural crest inducer, Wnt signals can induce neural crest cells in the absence of certain additives. In order to study earlier events in neural crest induction we have sought the expression of known neural crest markers during progressively earlier stages. We have identified the expression and requirement of Pax7 for neural crest formation during gastrulation. We also identified an earlier epiblast domain containing cells that generate neural crest cells when cultured in isolation under neural conditions. Taken together, these data suggest that neural crest specification is initiated during gastrulation and that Pax7 plays a critical role in its development. Multiple events account for the formation of neural crest cells in the chick embryo, along with previously identified BMP signals, Wnt signals seem also critical for the formation of neural crest cells. The transcription factor Pax7 is an early marker of the origin of neural crest cells in early gastrulating chick embryos, and its function is required for the formation of neural crest cells in different locations. [ABSTRACT FROM AUTHOR]

Objective: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease that may not always be related to the presence of traditional cardiovascular risk factors. The aim of this study was to determine if anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with cardiovascular disease in patients with RA., Methods: Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay in the earliest serum sample available from 937 patients with a diagnosis of RA. We studied the relationship between anti-CCP antibodies with traditional cardiovascular risk factors and cardiovascular events., Results: We found positive anti-CCP antibodies (>25 units/ml) in 672 patients (71.7%). There was no association between the anti-CCP antibodies and cardiovascular risk factors such as smoking, hypertension, dyslipidemia, being overweight, or diabetes mellitus. However, patients who had positive anti-CCP antibodies experienced more frequent ischemic heart disease (6.5% versus 2.6%; odds ratio [OR] 2.58, 95% confidence interval [95% CI] 1.17-5.65) and had higher mortality rates (11.2% versus 6.8%; OR 1.72, 95% CI 1.01-2.91). Similar results were obtained when we considered anti-CCP titers 20-fold higher (>500 units/ml). Multivariable analysis showed that ischemic heart disease is independently associated with positive anti-CCP antibodies (OR 2.8, 95% CI 1.19-6.56; P = 0.009)., Conclusion: Anti-CCP antibodies in patients with RA are independently associated with the development of ischemic heart disease.