Valentina Casieri, Silvia Agostini and Vincenzo Lionetti Pages 3 - 10 ( 8 )
The term "Epigenetics" refers to chromatin-based pathways involved in the regulation of gene expression without altering DNA sequence. Suppression of angiogenesis may be related to cardiac dysfunction following alterations in capillary microvasculature. An understanding of the relationship between angiogenesis and cardiac remodeling remains the major limitation in order to address the weak self-renewal ability of the adult failing heart. In physiological conditions, genes responsible for sustaining the angiogenic ability of the mature endothelial cells can be categorized into pro- and anti-angiogenic genes. The balanced expression of angiogenic genes maintains a state of equilibrium in capillary density of the adult myocardium. In the context of post-ischemic myocardial dysfunction, transcriptional and posttranscriptional modifications of the gene pool are involved in alterations of angiogenic balance in capillary microvasculature, angiogenesis, myocardial perfusion/contractility match and contractile function. The regulation of angiogenic gene expression by different epigenetic modifications may induce the formation of new vessels from coronary mature endothelial cells rather than endothelial progenitor cells. The role of proangiogenic epigenetic activators is emerging as a new actor in the modulation of the angiogenic balance of failing heart. In fact, the development of an ideal method to promote myocardial revascularization, while attenuating cardiac remodeling, is still a challenging issue. The present review will examine emerging studies on the epigenetic mechanisms involved in the regulation of function and angiogenic ability of mature endothelial cells residing in the adult myocardium.
Angiogenesis, endothelial cells, epigenetics, heart, heart failure.
, , Laboratory of Medical Science, Institute of Life Sciences, Scuola Superiore Sant’Anna, Via G. Moruzzi, 1, 56124 – Pisa, Italy.