Telomere dynamics during aging in polygenic left ventricular hypertrophy.

Short telomeres are associated with increased risk of cardiovascular disease. Here we studied cardiomyocyte telomere length at key ages during the ontogeny of cardiac hypertrophy and failure in the hypertrophic heart rat (HHR), and compared these with the normal heart rat (NHR) control strain. Key ages corresponded with the pathophysiological sequence beginning with fewer cardiomyocytes (2-days), leading to left ventricular hypertrophy (LVH) (13-weeks) and subsequently progression to heart failure (38-weeks). We measured telomere length, tissue activity of telomerase, mRNA levels of telomerase reverse transcriptase (Tert) and telomerase RNA component (Terc), and expression of the telomeric regulator microRNA miR-34a. Cardiac telomere length was longer in the HHR compared to the control strain at 2-days and 38-weeks, but shorter at 13-weeks. Neonatal HHR had higher cardiac telomerase activity and expression of Tert and miR-34a. Telomerase activity was not different at 13- or 38-weeks. Tert mRNA and Terc RNA were over-expressed at 38-weeks, while miR-34a was over-expressed at 13-weeks but down-regulated at 38-weeks. Circulating leukocytes were strongly correlated with cardiac telomere length in the HHR only. The longer neonatal telomeres in HHR are likely to reflect fewer foetal and early postnatal cardiomyocyte cell divisions and explain the reduced total cardiomyocyte complement that predisposes to later hypertrophy and failure. Although shorter telomeres were a feature of cardiac hypertrophy at 13-weeks, they were not present at the progression to heart failure at 38-weeks.