Hypertension is a complex, multifactorial disease that involves the coexistence of multiple risk factors, environmental factors and physiological systems. The complexities extend to the treatment and management of hypertension, which are still the pursuit of many researchers. In the last two decades, various genes have emerged as possible biomarkers and have become the target for investigations of specialized drug design based on its risk factors and the primary cause. Owing to the growing technology of microarrays and next-generation sequencing, the non-protein-coding RNAs (ncRNAs) have increasingly gained attention, and their status of redundancy has flipped to importance in normal cellular processes, as well as in disease progression. The ncRNA molecules make up a significant portion of the human genome, and their role in diseases continues to be uncovered. Specifically, the cellular role of these ncRNAs has played a part in the pathogenesis of hypertension and its progression to heart failure. This review explores the function of the ncRNAs, their types and biology, the current update of their association with hypertension pathology and the potential new therapeutic regime for hypertension.

Background: KCNMA1 encodes the α-subunit of the large-conductance Ca ²⁺ -activated K ⁺ channel, K _Ca 1.1, and lies within a linkage interval for atrial fibrillation (AF). Insights into the cardiac functions of K _Ca 1.1 are limited, and KCNMA1 has not been investigated as an AF candidate gene. Methods: The KCNMA1 gene was sequenced in 118 patients with familial AF. The role of K _Ca 1.1 in normal cardiac structure and function was evaluated in humans, mice, zebrafish, and fly. A novel KCNMA1 variant was functionally characterized. Results: A complex KCNMA1 variant was identified in 1 kindred with AF. To evaluate potential disease mechanisms, we first evaluated the distribution of K _Ca 1.1 in normal hearts using immunostaining and immunogold electron microscopy. K _Ca 1.1 was seen throughout the atria and ventricles in humans and mice, with strong expression in the sinus node. In an ex vivo murine sinoatrial node preparation, addition of the K _Ca 1.1 antagonist, paxilline, blunted the increase in beating rate induced by adrenergic receptor stimulation. Knockdown of the K _Ca 1.1 ortholog, kcnma1b , in zebrafish embryos resulted in sinus bradycardia with dilatation and reduced contraction of the atrium and ventricle. Genetic inactivation of the Drosophila K _Ca 1.1 ortholog, slo , systemically or in adult stages, also slowed the heartbeat and produced fibrillatory cardiac contractions. Electrophysiological characterization of slo -deficient flies revealed bursts of action potentials, reflecting increased events of fibrillatory arrhythmias. Flies with cardiac-specific overexpression of the human KCNMA1 mutant also showed increased heart period and bursts of action potentials, similar to the K _Ca 1.1 loss-of-function models. Conclusions: Our data point to a highly conserved role of K _Ca 1.1 in sinus node function in humans, mice, zebrafish, and fly and suggest that K _Ca 1.1 loss of function may predispose to AF.

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.