Transcription factors in heart: promising therapeutic targets in cardiac hypertrophy

Abstract

Regulation of gene expression is central to cell growth, differentiation and diseases. Context specific and signal dependent regulation of gene expression is achieved to a large part by transcription factors. Cardiac transcription factors regulate heart development and are also involved in stress regulation of the adult heart, which may lead to cardiac hypertrophy. Hypertrophy of cardiac myocytes is an outcome of the imbalance between prohypertrophic factors and antihypertrophic factors. This is initially a compensatory mechanism but sustained hypertrophy may lead to heart failure. The growing knowledge of transcriptional control mechanisms is helpful in the development of novel therapies. This review summarizes the role of cardiac transcription factors in cardiac hypertrophy, emphasizing their potential as attractive therapeutic targets to prevent the onset of heart failure and sudden death as they can be converging targets for current therapy.

Fig. (1)

General mechanism of cardiac hypertrophy and its effect on heart. Following a hypertrophic stimulus, there is an enhanced transcriptional activity of disease causing marker genes, and the consequential physiological changes including augmented protein synthesis, increased myocyte size, sarcomeric reorganization, reduction in the cardiac chamber size, and ventricular wall thickening. Both, Pro- Hypertrophic TFs and Anti-Hypertrophic TFs can be used as therapeutic targets to affect a block in the induction of hypertrophic signalling cascades, and hence preventing the manifestation of the disease.

Fig. (2).

Signaling pathways in cardiac hypertrophy leading to the transcriptional programming. The hypertrophic stimulus activates its corresponding receptor leading to a complex signaling cascade. Ultimately different signaling cascades converge on to a common program targeting the activity of certain transcription factors. This leads to activation of cardiac gene program in the nucleus which manifests finally as the hypertrophic phenotype.