Micro-RNA and mRNA myocardial tissue expression in biopsy specimen from patients with heart failure

doi:10.1016/j.ijcard.2015.07.043

International Journal of Cardiology

Volume 199, 15 November 2015, Pages 79-83

https://doi.org/10.1016/j.ijcard.2015.07.043 Get rights and content

Highlights

•
We explored miRNA expression in heart biopsy specimens with and without heart failure.
•
We explored miRNA and their related gene expression relationship.
•
Significant differences of RNA expression in apoptosis, hypertrophy and fibrosis

Abstract

Aims

There is increasing evidence that changes in microRNA (miRNA) expression occur in chronic heart failure and these may be involved in the pathogenesis. In this study we have explored the expression of selected myocyte and fibroblast-related microRNAs and messenger RNAs (mRNAs) that are associated with hypertrophy, apoptosis and fibrosis in biopsy specimens from patients with relatively new onset heart failure compared to a group of patients without heart failure.

Methods and Results

Myocardial biopsy specimens taken from Chinese patients presenting with recent heart failure were compared with a group of patients without heart failure undergoing routine cardiac surgery (n = 34). miRNAs (miR-1, -21, -23, -29, -30, -130, -133, -195, -199, -208, and -320) and corresponding mRNA expression were measured by real-time quantitative-PCR method. miR-1, -21, -23, -29, -130, -195 and -199 were significantly up-regulated in the heart failure group when compared to those without heart failure (all p < 0.01). However, miR-30, -133, -208 and -320 were not significantly different. Related mRNAs (casp3, coll I, coll III and TGF) were also significantly up-regulated (all p < 0.05) in the heart failure group.

Conclusion

Certain selected microRNAs involved in apoptosis, hypertrophy and fibrosis are up-regulated in the myocardium of patients with a clinical history of heart failure compared to those without. These specific miRNAs may be the most suitable for circulating biomarkers in the early stages of chronic heart failure and possibly future therapeutic targets.

Introduction

MicroRNAs (miRNAs) are a class of short, highly conserved, small noncoding RNAs which are important for many aspects of homeostasis and diseases [1], [2], [3], [4]. miRNAs regulate gene expression at post-transcriptional level by directing protein complexes to binding sites present on the 3′ untranslated region of targeted messenger RNA (mRNA), suppressing translation and/or inducing mRNA degradation. miRNAs can fine-tune mRNA abundance to keep the levels of mRNA within a physiological range [3], [4]. More than 2000 miRNAs have been identified in human cells and recently the number of studies on the involvement of miRNAs in cardiac pathology has increased rapidly [4]. In animal models they have been shown to be involved in hypertrophy, fibrosis, and apoptosis and the progression to heart failure (HF) [4], [5], [6], [7].

Ventricular remodeling is a major feature of chronic heart failure [8], [9]. During the remodeling progress, in response to pathological stimuli, the heart changes its shape and morphology. This process includes cardiomyocyte hypertrophy, apoptosis of cardiomyocyte and other cell types and collagen deposition [10]. There is increasing evidence to suggest that miRNAs are important in these processes of heart failure pathogenesis [11], [12]. Most of the published studies have used murine models for investigating the miRNA expression profile [13], [14]. In addition, work using whole peripheral blood has suggested that miRNAs are potential biomarkers for systolic heart failure [15], [16]. However, there are few data on miRNA expression within the myocardium of patients with heart failure. That which is available comes from studies done on explanted hearts taken at the time of transplantation [17], [18], [19] and there appears to be no data derived from myocardial biopsy tissue taken from patients with less extreme disease or early onset heart failure. Therefore in this study we have explored the expression of selected myocyte and fibroblast-specific miRNAs known to be involved in the processes of hypertrophy, apoptosis and fibrosis in myocardial biopsy specimens taken from patients admitted with heart failure compared with a group of patients without heart failure undergoing routine cardiac surgery. In addition specific mRNAs, which are targets of the individual miRNAs, were measured to determine if miRNA expression affected their co-related mRNAs.

Section snippets

Patients

Two groups of Chinese patients admitted into the Prince of Wales Hospital were studied. One group was admitted with symptoms and signs of recent onset heart failure (HF) due to possible myocarditis or dilated cardiomyopathy according to standard criteria [8], [9] who had transvenous right ventricular biopsy performed to rule out myocarditis. A second group of patients with or without signs of clinical HF had ventricular biopsies performed at the time of routine cardiac surgery (coronary artery

Patient demographics

Total RNA was isolated from 34 patients (17 with HF and 17 without HF). Mean age for the heart failure patients was 54 ± 10.3 years and for the non-failing heart patients was 59 ± 9.3 years. In both groups, 14 were male and 3 were female. Clinical features of patients with or without heart failure are given in Table 1. All the patients were taking some form of cardiac medication at the time of biopsy. The HF group were mainly on standard HF medications. Five of the HF group and 2 of the non-HF were

Discussion

In this study we have shown that the myocardium of patients with heart failure due to idiopathic dilated cardiomyopathy or ischemic heart disease had evidence of upregulation of certain miRNAs: miR -1, -21, -23, -29, -130, -195 and -199. However, miR-30, -133, -208 and -320 were not significantly different between the heart failure and control group. In addition, Casp3, coll I, coll III and TGF mRNA expression levels were significantly up-regulated in the patient group whereas CDC42, CDK 9,

Conclusion

In summary we have found significant differences for a range of microRNAs and gene expression involved in apoptosis, hypertrophy and fibrosis between the myocardium of patients with a clinical history of heart failure and those without. These results provide further insight into the role and mechanisms of these important processes in the development and progression of heart failure. In addition these results indicate which are the most promising miRNAs to explore as biomarkers of chronic heart

Funding

A research grant from the University Grants Committee of Hong Kong (RGC Research Fund 2140261) is acknowledged.

Conflict of interest statement

None declared.

Contributorship

JE Sanderson, MB Izzat and CM Yu, contributed to the original concept, planning, analysis of data, writing and editing. KB Lai contributed to the original concept, planning, analysis of data, writing, editing, establishing methods and undertaking experiments.

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^☆: The author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

¹: Current address: Damascus University Cardiac Surgery Hospital, Damascus, Syria.

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Micro-RNA and mRNA myocardial tissue expression in biopsy specimen from patients with heart failure☆

Highlights

Abstract

Aims

Methods and Results

Conclusion

Introduction

Section snippets

Patients

Patient demographics

Discussion

Conclusion

Funding

Conflict of interest statement

Contributorship

J. Am. Coll. Cardiol. Mar.

Lancet

Life Sci.

Am. J. Pathol.

J. Mol. Cell. Cardiol.

Int. J. Biochem. Cell Biol.

J. Biol. Chem.

J. Mol. Cell. Cardiol.

Cell. Signal.

MicroRNAs and beyond: the heart reveals its treasures

Hypertension

Introduction to the series on microRNAs in the cardiovascular system

Circ. Res.

MicroRNAs and cardiac pathology

Nat. Rev. Cardiol.

MicroRNAs in heart failure: is the picture becoming less miRky?

Circ. Heart Fail.

microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart

Genes Dev.

Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis

Proc. Natl. Acad. Sci. U. S. A.

The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes

J. Cell Sci.

Cardiac plasticity

N. Engl. J. Med.