On the epigenetics of vascular regulation and disease

Epigenetic alterations are chromatin-based modifications that affect the expression of genes without altering the DNA sequence itself. Such modifications include the methylation of DNA, the posttranslational modification of histone proteins and RNA-based mechanisms, [1] which may altogether modulate the tertiary structure and thus the accessibility of promoter DNA for transcription factors and numerous regulatory elements that finally affect transcription [2]. Epigenetic processes are essential as to the determination of cell identity and for the propagation of modifications that are meiotically and mitotically heritable [3]. In this context, epigenetic pathways are key elements in the regulation of endothelial gene expression, and thus in the pathogenesis of vascular disease such as atherosclerosis and vascular restenosis. The vascular system is highly flexible with regard to physiological and pathological challenges and carries therefore the potential to regenerate and generate new structures during the whole organismal life span on the basis of two major epigenetic principles: the heritable propagation of the information on changes in gene expression without alterations in the DNA sequence, and the capacity to develop different phenotypes from one single genotype [4].Since Conrad Waddington first coined the term “epigenetics” back in 1942 as the study about “the causal interactions between genes and their products, which bring the phenotype into being”, research progress since then led to an advanced definition [5]. More recently, epigenetics was redefined as the study of “stable alterations in gene expression without alterations in the genetic code itself” [6]. These alterations in gene expression are achieved by changes in the tertiary structure of the DNA strand and thus the accessibility of the DNA for molecules which effect gene expression. Under physiological conditions this machinery allows relatively fast heritable changes in gene expression in response t