Systemic hypertension, which eventually results in heart failure, renal failure or stroke, is a common chronic human disorder that particularly affects elders. Although many signaling pathways involved in the development of hypertension have been reported over the past decades, which has led to the implementation of a wide variety of anti-hypertensive therapies, one half of all hypertensive patients still do not have their blood pressure controlled. The frontier in understanding the molecular mechanisms underlying hypertension has now advanced to the level of epigenomics. Particularly, increasing evidence is emerging that DNA methylation and histone modifications play an important role in gene regulation and are involved in alteration of the phenotype and function of vascular cells in response to environmental stresses. This review seeks to highlight the recent advances in our knowledge of the epigenetic regulations and mechanisms of hypertension, focusing on the role of DNA methylation and histone modification in the vascular wall. A better understanding of the epigenomic regulation in the hypertensive vessel may lead to the identification of novel target molecules that, in turn, may lead to novel drug discoveries for the treatment of hypertension.

Vascular smooth muscle cells (VSMCs) are the stromal cells of the vascular wall and are responsible for regulating arterial tone, blood pressure, and blood supply of the tissues. VSMCs display diversity in function and phenotype depending on their location within the arterial tree (large conduit vs. small resistance vessels), their embryologic origin, and their organ-dependent microenvironment. The heterogeneity of VSMCs is regulated by multiple mechanisms including intracellular signaling and changes in the VSMC microenvironment. Genetic disorders and extrinsic stimuli-induced dysfunction in VSMCs are associated with age-related vascular pathogenesis and vascular diseases, and thus are considered as a potential therapeutic target.

Mitochondria play a key role in the normal functioning of the heart and in the pathogenesis and development of various types of heart disease. In addition, specific mitochondrial cardiomyopathies due to mutations in mitochondrial DNA have been identified. Increasing studies demonstrate that mitochondrial function has emerged as a therapeutic target in heart disease. This chapter addresses the recent studies of the role and the mechanism of mitochondria in the development of heart disease, and the progress in clinical diagnosis and treatments on a mitochondrial basis. Consequently, the aim of this chapter is to outline current knowledge about mitochondria in the heart disease.