Mechanisms Regulating Ribosomal Gene Transcription During Cardiac Hypertrophy

Funded Activity Summary

After birth the muscle cells of the human heart stop dividing. Subsequent growth of the heart is achieved by increasing the size of preexisting muscle cells. This process is referred to as hypertrophic growth and accounts for the difference in size between the juvenile and adult human heart. However later on in life, particularly during cardiovascular disease states such as high blood pressure, the adult heart may grow above and beyond that normally expected. This uncontrolled growth, results eventually in a sick heart which is no longer able to function properly. Such inappropriate growth of the heart is a component of many human cardiovascular disease states and contributes significantly to human morbidity and mortality. Regardless of the cause, hypertrophic growth of the heart results from increased protein synthesis. This is controlled by increased synthesis of ribosomes, the machinery responsible for making proteins. During the course of our studies investigating the regulation of heart muscle cell hypertrophy we have demonstrated that changes in the activity of a protein termed UBF, which is involved in regulating synthesis of ribosomes, correlates with the rate of hypertrophic growth. We have also demonstrated that if we artificially increase the amount of UBF protein in heart muscle cells we can stimulate hypertrophy. These finding indicate that alterations in the amount or activity of UBF may link hypertrophic stimuli to increased growth of the heart. The work described in this study proposes to investigate the signals and pathways which regulate the amount and activity of the UBF protein during hypertrophic growth of heart muscle cells. We hope by understanding the mechanisms by which the heart grows we will be able to design rational therapeutic regimens to combat the abnormal growth of the heart that often accompanies human cardiovascular disease states such as high blood pressure.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2005

Funding Scheme: NHMRC Project Grants

Funding Amount: $436,540.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Nutrigenomics and personalised nutrition

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

In vitro mutagenesis and gene therapy | cardiac hypertrophy | cardiac muscle hypertrophy | cardiomyocyte growth | cardiovascular disease | hypertension | ribosomal gene transcription | transcription factors regulation and promoter analysis

Related Links