Interplay of histone acetylation and transcription factors in cardiac hypertrophy

Authors:Ramachandran GR, Qureshi SF,Anantapur V, Nallari P
Int J Biol Med Res. 2011; 2(2): 581 – 588  |  PDF File

Abstract

Adult cardiac disease is the most frequent cause of mortality in the western world where death, as a result of heart failure, is more prevalent than all disorders combined. Heart failure can be defined as a deficiency in the ability of the heart to pump an adequate supply of blood around the body which can be exemplified by cardiomyopathies. Hypertrophic Cardiomyopathy results due to pathological thickening of the heart muscles(sarcomeres replicate) /cardiac hypertrophy. Several(around 600) mutations have been identified in sarcomeric as well as other modifier genes that precipitate Hypertrophic cardiomyopathy. Our lab has also identified several novel mutations in the sarcomeric genes in the Indian population which could correlate to the epigenetics of the genes.Epigenetic changes like histone acetylation and DNA methylation are transient and involves no base changes. Recently , multiple transcriptional pathways have been identified involved in cardiac hypertrophy along with epigenetic modifications . Here we have tried to concentrate upon the role of histone acetylation and associated transcription factors in cardiac hypertrophy with respect to Hypertrophic Cardiomyopathy for the identification of therapeutic targets in molecular pathways . We hypothesise that apart from the pathways reviewed below, several others are yet to be unearthed for a greater understanding. Of special interest is the fact that reactivation of fetal genes leads to cardiac hypertrophy which is possible due to the interplay of transcription factors and histone acetyl transferase/histone deacetylases . Also, the pathways are highly complex since some classes of HDAC promote hypertrophy while others repress . Several therapeutic targets have been identified and many drugs against HCM are in variable stages of clinical trials with respect to histone deacetylases and transcription factors.