S, and is responsible for the 5 million americans with insufficient cardiac function. Circulating microrna30d is associated with response to. Microrna34a regulates cardiac ageing and function nature. Here we show that mir 34a is induced in the ageing heart and that in vivo silencing or genetic deletion of mir 34a reduces age associated cardiomyocyte cell. Stem cells have great potential in clinical therapy due to their pluripotency and selfrenewal ability. In the vasculature, sirt1 also regulates endothelial cell function through its action as a deacetylase.
The p53mir34 axis in development and disease oxford. Jul 17, 2019 cardiac stem cells cscs exhibit agedependent characteristics. Sutherland,1 xiaoxia qi,1 laurent gautron, 2joel k. Microrna34a regulates cardiac ageing and function pubmed. Suppression of mir34a expression in the myocardium protects. Micrornas in cardiovascular ageing the physiological society. Microrna 34a regulates cardiac ageing and function. Furthermore, the role of mir34a in regulating endogenous cardiac regeneration in.
Of the mirnas tested, the level of mir 34a is upregulated in fxrnull mice. Novel microrna prosurvival cocktail for improving engraftment and function of cardiac progenitor cell transplantation. We investigated the effects of mir34a on heart function after ischemiareperfusion ir injury. T1 circulating microrna 30d is associated with response to cardiac resynchronization therapy in heart failure and regulates cardiomyocyte apoptosis a translational pilot study. May 11, 2017 stem cells are undifferentiated cells and have multilineage differentiation potential. Ageing affects cardiac function in multiple manners. Absence of mutation in mir34a gene in a chinese longevity population. Several mirs have been described to be regulated during ageing and some of these mirs are involved in the regulation of ageing. Background although microrna mirna regulates initiation and or progression of atrial fibrillation af in canine af models, the underlying mechanism in humans remains unclear. Old ocscs showed decreased differentiation and proliferation capacities as compared to young ycscs, the.
Regenerative therapies could be particularly beneficial for heart disease, which is the leading killer of adults in the u. China 1 key laboratories of education ministry for myocardial. Microrna34a mir34a is expressed in the myocardium and expression is altered after myocardial injury. Next to cancer, mir 34a is recently found to be implicated in cardiovascular disease as one damager factor. Aug 06, 2010 these findings support our idea that mir 34a regulates senescence in endothelial cells. Hu s, huang m, nguyen pk, gong y, li z, jia f, lan f, liu j, nag d, robbins rc, wu jc. Recent evidence suggests that mirnas are differentially expressed in the failing myocardium and play an important role in progression of heart failure by targeting genes that govern diverse functions in cardiac remodeling process. However, oncologists are concerned by the risk of long term treatment side effects, including congestive heart failure chf. Roles of microrna34a targeting sirt1 in mesenchymal stem. Microrna9 regulates cardiac fibrosis by targeting pdgfr. In the present study, we investigated whether sirt1related mirs, including mir9, mir 34a, mir2, mir181a, mir195, mir199a, mir199b and mir204. Olson1, 1department of molecular biology 2department of internal medicine. Hypothalamic stem cells control ageing speed partly through. We propose that altered expression of mirnas in the heart during ageing contributes to the agedependent decline in cardiac function.
Human circulating microrna1 and microrna126 as potential. For example, it is known that microrna 21 is only weakly upregulated in normal healthy hearts, but is markedly upregulated in most models of heart failure and enlargement, which suggests microrna 21 plays a key role in this condition. Role of micrornas in cardiac remodeling and heart failure. Regulation of microrna expression and function by nuclear. Tanshinone iia protects against sudden cardiac death induced by lethal arrhythmias via repression of microrna 1. Aging has a remarkable impact on the function of the heart, and is independently associated with.
Plasma levels of ctnt, ntprobnp, sst2 and 10 selected mirnas were measured in a total of 45 breast cancer patients receiving anthracyclines as part of their neoadjuvant chemotherapy nac. Increased expression of sirtuins lowers the risk of agerelated diseases, while their role. Microrna5a regulates sodiumcalcium exchanger gene expression and cardiac electrical activity eric duong, bsc, jiening xiao, phd, xiao yan qi, phd, stanley nattel, md, fhrs from the department of pharmacology and therapeutics, mcgill university, montreal, canada. Effect of aging and sex on circulating micrornas in humans. Pdf microrna34a regulates cardiac ageing and function. Microrna 34a regulates the longevityassociated protein sirt1 in coronary artery disease. Research open access regulation of cardiac micrornas by serum. We speculated that certain mirnas in atrial tissue are related to af, and evaluated the relationship of mirna expression in human atrial tissue in cardiac surgery patients. In the heart, genetic ablation of mir 34a mitigates contractile function decline and prevents cardiac hypertrophy of old mice reducing cardiomyocytes apoptosis 14. It regulates a wide range of genes and pathways involved in cancer initiation, progression and metastasis. In the long term, age related cardiovascular diseases cvds.
Seminal work has recently demonstrated that mir 34a is induced in the ageing heart and in vivo silencing or genetic deletion of mir 34a reduces ageassociated cardiomyocyte cell death. In the long term, agerelated cardiovascular diseases cvds. Further, mir 34a expression rises in the border zone of the infarcted heart and its inhibition improves remodeling after infarction 14. Microrna profiling implicates the insulinlike growth factor. Despite improvements in diagnosis and treatment, many elderlies suffer from cardiovascular problems that are much more frequent in an older, more fragile organism. Increased apoptosis and premature cellular ageing of the diabetic heart underpin the. It also regulates normal functions including cell differentiation and organ development. A prolonged qrs often corresponds to a bundlebranch block and can increase the risk of sudden death in humans. Microrna34a induces vascular smooth muscle cells senescence. Cited2 has been implicated in the regulation of heart development. Cited2 mrna and protein level was downregulated in aging heart tissue and cscs. Microrna34a regulates the longevityassociated protein sirt1. Pdf microrna in cardiovascular aging and agerelated. Noncoding rnas ncrnas are a class of rna molecules that do not encode proteins.
Shikonin inhibits adipogenic differentiation via regulation. Alcendor rr, gao s, zhai p, zablocki d, holle e, yu x, et al sirt1 regulates aging and resistance to oxidative stress in the heart. A cardiac microrna governs systemic energy homeostasis by regulation of med chad e. Microrna profiling unveils hyperglycaemic memory in the. Variations of circulating cardiac biomarkers during and after.
Frontiers involvement of microrna34a in agerelated. Microrna34a regulation of endothelial senescence sciencedirect. Endothelial senescence is thought to play a role in cad coronary artery disease. Frontiers microrna in cardiovascular aging and age. The aging retinal pigment epithelium and oxidative stress, mediated by reactive oxygen species ros accumulation, have been implicated in the mechanisms of agerelated macular degeneration amd. For example, mir34a has been shown to regulate cardiac function and ageing, in part through affecting fibrosis in this tissue and mir26a can. Absence of mutation in mir34a gene in a chinese longevity populationj.
Pdf microrna34a regulates cardiac aging and function. However, the role of srf in the regulation of microrna expression and microrna. Idiopathic pulmonary fibrosis is a disease characterized by alveolar epithelial cell injury, inflammatory cell infiltration and deposition of extracellular matrix in lung tissue. Nov 01, 2015 read the master switchers in the aging of cardiovascular system, reverse senescence by microrna signatures. We propose that altered expression of mirnas in the heart during ageing contributes to the age dependent decline in cardiac function. Microrna34a regulates cardiac aging and function article pdf available in nature 4957439.
A role is demonstrated for mir 34a, a microrna that is upregulated in the ageing heart. Micrornas mirnas have been reported as potentially being useful biomarkers for various diseases including cancer, diabetes mellitus, heart disease, neurological disease and agerelated diseases. Elevated levels of mir34a were observed in the islets of diabetic mice, and were induced in sensitization to. Sirt1, a class iii histone deacetylase, has been implicated in the regulation of cellular metabolism, senescence, and longevity.
Cited2 regulates proliferation and survival in young and old. Generally, stem cells are classified into adult stem cells, embryonic stem cells escs and induced pluripotent stem cells ipscs. Mar 07, 20 together, these results identify ageinduced expression of mir 34a and inhibition of its target pnuts as a key mechanism that regulates cardiac contractile function during ageing and after acute myocardial infarction, by inducing dna damage responses and telomere attrition. Noncoding rnas in cardiac aging fulltext cellular physiology. The expression level of the adapter protein p66shc, a key protein that regulates cellular oxidative stress, is relatively low under normal conditions because of the effects of silent mating type. Article information, pdf download for mir34a and mir9 are. Jan 29, 2018 over time, the chance of cure after the diagnosis of breast cancer has been increasing, as a consequence of earlier diagnosis, improved diagnostic procedures and more effective treatment options. The aim of the present study is to evaluate the variations of innovative biomarkers during and after anthracyclinecontaining chemotherapy.
The master switchers in the aging of cardiovascular system. Diabetes induces the activation of proageing mir34a in the heart. The musclespecific microrna mir1 regulates cardiac arrhythmogenic potential by targeting gja1 and kcnj2. Jul 26, 2017 it has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Micrornas in cardiovascular ageing seeger 2016 the. In this study, we evaluated innovative circulating cardiac biomarkers. Microrna24 regulates vascularity after myocardial infarction. Absence of mutation in mir34a gene in a chinese longevity. Treatment of cultured neonatal rat cfs with pdgfbb or serum suppressed the expression of mir9. As mouse models of bleomycininduced pulmonary fibrosis display many of the same phenotypes observed in patients with idiopathic pulmonary fibrosis, they have been used to study various aspects of the disease. Microrna34a plays a key role in cardiac repair and.
For example, mir 34a has been shown to regulate cardiac function and ageing, in part through affecting fibrosis in this tissue and mir26a can also affect cardiac fibrosis through altering collagen i levels. Research open access regulation of cardiac micrornas by serum response factor xiaomin zhang, gohar azhar, scott a helms, jeanne y wei abstract serum response factor srf regulates certain micrornas that play a role in cardiac and skeletal muscle development. In addition, ageinduced expression of mir34a regulates cardiac aging and function. Inhibition of microrna 21 reduces fibrosis scarring, heart enlargement and improves cardiac function. Frontiers microrna in cardiovascular aging and agerelated. Fxr is the primary biosensor for endogenous bile acids and regulates the expression of numerous genes involved in lipid and glucose metabolism.
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