MicroRNA-34a and tert act as epi-drivers of cardiac telomere length and polygenic cardiac hypertrophy
- Authors: Booth, Scott , Marques, Francine , Prestes, Priscilla , Curl, Claire , Delbridge, Lea , Lewandowski, Paul , Harrap, Stephen , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Heart, Lung and Circulation Vol. 24, no. S3 (2015), p. S180-S181
- Full Text: false
- Reviewed:
- Description: Cardiac hypertrophy is one of the main risk factors forheart failure. Here we aimed to investigate whether cardiactelomere length contributes to polygenic cardiac hypertro-phy independent of blood pressure. We also investigatedwhether changes in telomere length were due to the telomereregulators microRNA-34a,Ppp1r10(also known asPnuts)and telomerase. We used the hypertrophic heart rat (HHR),a normotensive model of polygenetic cardiac hypertrophy,and compared it to age-matched controls. Telomere length, microRNA levels, gene expression and telomerase activitywere measured in isolated cardiomyocytes and left ventricletissue using real-time PCR. Telomere length was significantlylonger in 2-day and 38-week-old HHR, but shorter at 4-and 13-week HHR. In the HHR, telomere length becameshorter early in development, while in the control straintelomere shortening was only observed in late adulthood.Telomere length was the main determinant of cardiac mass.
Cardiac telomere length in heart development, function, and disease
- Authors: Booth, Scott , Charchar, Fadi
- Date: 2017
- Type: Text , Journal article , Review
- Relation: Physiological Genomics Vol. 49, no. 7 (2017), p. 368-384
- Relation: http://purl.org/au-research/grants/nhmrc/1034371
- Full Text: false
- Reviewed:
- Description: Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. © 2017 the American Physiological Society.
The emerging role of non-coding RNA in essential hypertension and blood pressure regulation
- Authors: Marques, Francine , Booth, Scott , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Human Hypertension Vol. 29, no. 8 (2015), p. 459-467
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text: false
- Reviewed:
- Description: Unravelling the complete genetic predisposition to high blood pressure (BP) has proven to be challenging. This puzzle and the fact that coding regions of the genome account for less than 2% of the entire human DNA support the hypothesis that genetic mechanism besides coding genes are likely to contribute to BP regulation. Non-coding RNAs (ncRNAs) are emerging as key players of transcription regulation in both health and disease states. They control basic functions in virtually all cell types relevant to the cardiovascular system and, thus, a direct involvement with BP regulation is highly probable. Here, we review the literature about ncRNAs associated with human BP and essential hypertension, highlighting investigations, methodology and difficulties arising in the field. The most investigated ncRNAs so far are microRNAs (miRNAs), small ncRNAs that modulate gene expression by posttranscriptional mechanisms. We discuss studies that have examined miRNAs associated with BP in biological fluids, such as blood and urine, and tissues, such as vascular smooth muscle cells and the kidney. Furthermore, we review the interaction between miRNA binding sites and single nucleotide polymorphisms in genes associated with BP. In conclusion, there is a clear need for more human and functional studies to help elucidate the multifaceted roles of ncRNAs, in particular mid- and long ncRNAs in BP regulation. © 2015 Macmillan Publishers Limited All rights reserved.