MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure.
نویسندگان
چکیده
BACKGROUND Chronic heart failure is characterized by left ventricular remodeling and reactivation of a fetal gene program; the underlying mechanisms are only partly understood. Here we provide evidence that cardiac microRNAs, recently discovered key regulators of gene expression, contribute to the transcriptional changes observed in heart failure. METHODS AND RESULTS Cardiac transcriptome analyses revealed striking similarities between fetal and failing human heart tissue. Using microRNA arrays, we discovered profound alterations of microRNA expression in failing hearts. These changes closely mimicked the microRNA expression pattern observed in fetal cardiac tissue. Bioinformatic analysis demonstrated a striking concordance between regulated messenger RNA expression in heart failure and the presence of microRNA binding sites in the respective 3' untranslated regions. Messenger RNAs upregulated in the failing heart contained preferentially binding sites for downregulated microRNAs and vice versa. Mechanistically, transfection of cardiomyocytes with a set of fetal microRNAs induced cellular hypertrophy as well as changes in gene expression comparable to the failing heart. CONCLUSIONS Our data support a novel mode of regulation for the transcriptional changes in cardiac failure. Reactivation of a fetal microRNA program substantially contributes to alterations of gene expression in the failing human heart.
منابع مشابه
Harnessing fetal and adult genetic reprograming for therapy of heart disease.
Heart is the first organ formed during organogenesis. The fetal heart undergoes several structural and functional modifications to form the four-chambered mammalian heart. The adult heart shows different adaptations during compensatory and decompensatory heart failure. However, one common adaptation in the pathological heart is fetal reprogramming, where the adult heart expresses several genes ...
متن کاملEvaluation of intravenous injection of amniotic membrane stem cells to reduce inflammatory factors in heart failure
Background: Heart failure is one of the most common cardiovascular disorders and is considered a chronic, progressive and debilitating disorder. The medical treatment of this disease is accompanied by many problems. Today, stem cells are being used increasingly to reduce the problems of heart failure treatments. Since pro-inflammatory cytokines play an important role in the prognosis and progre...
متن کاملA New Minimum Order Lumped-Parameter Model of Circulatory System for Patients with Suffered Left and Right-Sided Heart Failure
In this study a new minimum lumped electrical model of total circulatory system through numerical solutions to approximate the response of the human circulatory system was presented. Among five existent ventricular elastances as activity function of heart pumps, a more accurate model was chosen as well as the operation of baroreflex system to accommodate variations in heart rate and systemic va...
متن کاملThe effect of aerobic exercise on MMP-2 / miR-21 signaling pathway of cardiac fibrosis in elderly rats
Background :The concept of survival has changed since the twentieth century to guarantee quality of life in the twenty-first century (1). Aging is associated with a certain degree of interstitial fibrosis, which progresses to heart failure. Therefore, finding new and practical methods is an important and necessary help to reduce heart tissue fibrosis in the elderly (2). Providing mechanisms by ...
متن کاملLetter to the Editor: "Evaluate the effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina"
Dear editor In a recent issue of the journal, Dastani et al. (2019) evaluate the effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina. Despite the fact that the topic was interesting, there were some defects and we wish to call to your attention important factual issues in this publication. The most cr...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Circulation
دوره 116 3 شماره
صفحات -
تاریخ انتشار 2007