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 wk) and subsequently progression to heart failure (38 wk). 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 with the control strain at 2 days and 38 wk, but shorter at 13 wk. Neonatal HHR had higher cardiac telomerase activity and expression of Tert and miR-34a. Telomerase activity was not different at 13 or 38 wk. Tert mRNA and Terc RNA were overexpressed at 38 wk, while miR-34a was overexpressed at 13 wk but downregulated at 38 wk. Circulating leukocytes were strongly correlated with cardiac telomere length in the HHR only. The longer neonatal telomeres in HHR are likely to reflect fewer fetal 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 wk, they were not present at the progression to heart failure at 38 wk.
School of Applied and Biomedical Sciences, Faculty of Science and Technology, Federation University Australia, Victoria, Australia;
Francine Z
FZ
Marques
School of Applied and Biomedical Sciences, Faculty of Science and Technology, Federation University Australia, Victoria, Australia;
Scott A
SA
Booth
School of Applied and Biomedical Sciences, Faculty of Science and Technology, Federation University Australia, Victoria, Australia;
Priscilla R
PR
Prestes
Department of Physiology, University of Melbourne, Victoria, Australia; and.
Claire L
CL
Curl
Department of Physiology, University of Melbourne, Victoria, Australia; and.
Lea M D
LM
Delbridge
School of Medicine, Deakin University, Victoria, Australia.
Paul
P
Lewandowski
Department of Physiology, University of Melbourne, Victoria, Australia; and.
Stephen B
SB
Harrap
School of Applied and Biomedical Sciences, Faculty of Science and Technology, Federation University Australia, Victoria, Australia; f.charchar@federation.edu.au.
Fadi J
FJ
Charchar
D000375:Aging / Q000473:pathology*; D000818:Animals; D006332:Cardiomegaly / Q000150:complications / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006352:Heart Ventricles / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D020412:Multifactorial Inheritance / Q000235:genetics*; D009929:Organ Size; D011916:Rats, Inbred F344; D012044:Regression Analysis; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
D004268:DNA-Binding Proteins; C560944:MIRN34 microRNA, rat; D035683:MicroRNAs; D019098:Telomerase
Terc; Tert; cardiac hypertrophy; development; left ventricular hypertrophy; miRNA; telomerase; telomeres