Significant progress has been made in the clinical management of a variety of cardiovascular diseases. Nevertheless, the therapeutic efficacy of the current treatment modalities for atherosclerosis and restenosis is not fully sufficient in a large proportion of patients. One of the major contributing factors is the clinical and biological heterogeneity of these still life-threatening diseases, which involve processes that we do not fully understand at the moment. Over the past decades, it has become increasingly clear that part of the gene-environmental interactions relevant for complex diseases is regulated by epigenetic mechanisms such as histone acetylation and DNA methylation. Epigenetic processes modulate gene expression patterns without modifying the actual DNA sequence and have profound effects on the cellular repertoire of expressed genes. They contribute to the expression of genes that play a key role in extracellular matrix formation, inflammation, and proliferation, processes involved in cardiovascular pathologies such as atherosclerosis and restenosis. Therefore, in this review, we argue that epigenetic regulators involved in histone acetylating and deacetylating activities contribute to the pathogenesis of atherosclerosis and restenosis. Furthermore, as alterations in chromatin structure are reversible, these epigenetic modifications are amendable to pharmacological intervention, which may prove to be an effective treatment modality for the management of cardiovascular diseases.
These results demonstrate differences between non-asthmatic and asthmatic subjects in the basal levels of nasal cytokines and their inhibitors, and in the effect of experimental RV-infection on these levels. The results indicate that RV may enhance inflammation more markedly in asthmatics, and suggest that this may in part be explained by lower IL-1ra levels. In addition, the observation that budesonide-treatment may result in higher nasal IL-1ra levels supports the hypothesis that steroids act in part by increasing the endogenous anti-inflammatory screen.
Introduction. The FSAP-Marburg I polymorphism (1704G > A), which reduces FSAP activity, is associated with late complications of carotid stenosis in humans. Therefore, this study examines the influence of the Marburg I polymorphism and the closely linked Marburg II polymorphism (1280G > C) on various cardiovascular outcomes in two large independent study populations. Methods. The two Marburg polymorphisms in the HABP2 gene encoding FSAP were genotyped in a large population of elderly patients at risk for vascular disease (the PROSPER-study, n = 5804) and in a study population treated with a percutaneous coronary intervention (the GENDER-study, n = 3104). Results. In the PROSPER study, the Marburg I polymorphism was associated with an increased risk of clinical stroke (HR: 1.60, 95% CI: 1.13–2.28) and all-cause mortality (HR: 1.33, 95% CI: 1.04–1.71). In the GENDER study carriers of this variant seemed at lower risk of developing restenosis (HR: 0.59, 95% CI: 0.34–1.01). The Marburg II polymorphism showed similar but weaker results. Conclusion. The increase in stroke risk in Marburg I carriers could be due to differential effects on smooth muscle cells and on matrix metalloproteinases, thereby influencing plaque stability. The possible protective effect on restenosis could be the result of reduced activation of zymogens, which are involved in hemostasis and matrix remodeling.
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