The Australian Genetic Heart Disease Registry: The First Five Years

Telomeres – the specialised DNA–protein structures at the ends of eukaryotic chromosomes, are essential for maintaining genome stability and integrity. Although shorter telomere length in circulating leukocytes has been previously associatedwith cardiovascular disease and cardiac mass in humans, telomere length in heart tissue in cardiac hypertrophyhas never been studieddue to the difficulty of acquiring relevant tissue samples. Our aim was to investigate the telomere length in theheart and circulating leukocytes of a genetic model of cardiac hypertrophy, the Hypertrophic Heart Rat (HHR), at 13–16 weeks old, when it presents with established hypertrophy compared to normal control strain. DNA was extracted from heart and circulating leukocytes (n= 7 HHR and n= 6 controls from the Normal Heart Rat strain) using the PureLink® Genomic Extraction kit, and relative telomere length was measured by real-time PCR (qPCR) based on the Telomere-to-SingleCopyGene (T/S) ratiomethod. Telomeres were significantly shorter in the heart (P= 0.002) and circulating leukocytes (P= 0.001) of the HHR compared to the control strain. Heart and circulating leukocytes telomere lengthwere highly correlated (r= 0.571, P= 0.02), while there was a negative correlation between cardiac weight index and telomere length in the heart (r=−0.57, P= 0.02) and circulating leukocytes (r=−0.72,P= 0.003). Thesefindings suggest that telomeres may be a hallmark of cardiac cells in hypertrophy, and it validates the use of circulating leukocytes as a marker for telomere length in the heart. We are currently investigating the contribution of shorter telomeres to the development of hypertrophy in this rat model.