Function and Therapeutic Potential of Noncoding RNAs in Cardiac Fibrosis

Creemers, Esther E.; Rooij, Eva van

doi:10.1161/circresaha.115.305242

Cited by 98 publications

(64 citation statements)

References 96 publications

(120 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The etiology of the fibrogenic cardiac phenotype is still being elucidated, but recent studies have demonstrated that in addition to canonical TGFβ fibrotic signaling molecules, several miRNAs contribute to myocardial fibrosis in the pressure-overloaded myocardium 25, 26, 47 . In vivo silencing of miR-21 suppresses ERK-MAP kinase fibrotic signaling and prevents cardiac dysfunction in a mouse pressure-overload-induced disease model.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-10 Inhibits Bone Marrow Fibroblast Progenitor Cell–Mediated Cardiac Fibrosis in Pressure-Overloaded Myocardium

et al. 2017

View full text Add to dashboard Cite

Background Activated fibroblasts (myofibroblasts; myoFBs) play critical role in cardiac fibrosis; however, their origin in the diseased heart remains unclear warranting further investigation. Recent studies suggest the contribution of bone marrow fibroblast progenitor cells (BM-FPC) in pressure overload (PO)-induced cardiac fibrosis. We have earlier shown that interleukin-10 (IL10) suppresses PO-induced cardiac fibrosis; however, the role of IL10 in inhibition of BM-FPC-mediated cardiac fibrosis is not known. We hypothesized that IL10 inhibits PO-induced homing of BM-FPCs to the heart and their trans-differentiation to myoFBs and thus attenuates cardiac fibrosis. Methods Pressure overload was induced in wild-type (WT) and IL10 knockout (IL10KO) mice by transverse aortic constriction (TAC). To determine the bone marrow origin, chimeric mice were created using eGFP WT mice marrow to the IL10KO mice. For mechanistic studies, fibroblast progenitor cells were isolated from mouse bone marrow. Results Pressure overload enhanced bone marrow fibroblast progenitor cell (BM-FPC) mobilization and homing in IL10KO mice compared to WT mice. Furthermore, WT bone marrow (from eGFP mice) transplantation in BM-depleted IL10KO mice (IL10KO chimeric mice) reduced TAC-induced BM-FPC mobilization compared to IL10KO mice. GFP co-staining with αSMA or collagen 1α in left ventricular tissue sections of IL10KO chimeric mice suggest that myofibroblasts were derived from bone marrow post-TAC. Finally, WT-BMT in IL10KO mice inhibited TAC-induced cardiac fibrosis and improved heart function. At the molecular level, IL10 treatment significantly inhibited TGFβ-induced transdifferentiation and fibrotic signaling in WT BM-FPC in vitro. Furthermore, fibrosis-associated miRNAs expression was highly upregulated in IL10KO-FPCs compared to WT-FPCs. PCR-based selective miRNA analysis revealed that TGFβ-induced enhanced expression of fibrosis-associated miRNAs (miRNA-21, -145 and -208) was significantly inhibited by IL10. Restoration of miRNA-21 levels suppressed the IL10 effects on TGFβ-induced fibrotic signaling in BM-FPC. Conclusion Our findings suggest that IL10 inhibits BM-FPC homing and trans-differentiation to myofibroblasts in pressure overloaded myocardium. Mechanistically for the first time we showed that IL10 suppresses Smad-miRNA-21 mediated activation of BM-FPCs and thus modulates cardiac fibrosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Interleukin-10 Inhibits Bone Marrow Fibroblast Progenitor Cell–Mediated Cardiac Fibrosis in Pressure-Overloaded Myocardium

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Other studies have identified numerous additional miRNAs dysregulated in cardiac fibrotic models. miRNAs implicated in regulating fibrosis based on in vivo studies [knockout models, transgenics, gene delivery (AAV/adenovirus) and miRNA oligonucleotide based (antimiR/antagomiR)] include miR-29, miR-15, miR34a, miR-101, miR-132, miR-1, mR-133, miR-208a, miR199b, miR-22 and miR-489 (15). These other pro-fibrotic miRNAs may act via similar or separate pathways to miR-433 in the heart.…”

Section: Other Mirnas Implicated In Regulating Cardiac Fibrosismentioning

confidence: 99%

Therapeutic potential of targeting microRNAs to regulate cardiac fibrosis: miR-433 a new fibrotic player

Ooi¹,

Bernardo²,

McMullen³

2016

Ann. Transl. Med.

View full text Add to dashboard Cite

“…The expression pattern of miRNAs can provide information about the pathophysiological processes underlying HF, such as myocardial fibrosis and hypertrophy [5, 15, 16]. For example, Duisters et al [17] showed that both miR-133 and miR-30 directly downregulate connective tissue growth factor, which is associated with myocardial fibrosis [8, 17].…”

Section: Discussionmentioning

confidence: 99%

Association of miR-197-5p, a Circulating Biomarker for Heart Failure, with Myocardial Fibrosis and Adverse Cardiovascular Events among Patients with Stage C or D Heart Failure

Liu

Zheng²,

Dong

et al. 2018

Cardiology

View full text Add to dashboard Cite

Objective: The aim of this study was to identify heart failure (HF)-specific circulating micro-RNAs (miRNA), and examine whether the selected miRNAs correlate with myocardial fibrosis and are reflective of the incidence of adverse cardiovascular events in patients with stage C or D HF. Methods: Circulating miRNAs which were expressed in end-stage HF patients and matched healthy controls were detected by microarray analysis and validated by quantitative real-time polymerase chain reaction. Multivariate Cox regression analysis was performed to determine whether the selected circulating miRNAs could be prognostic factors in HF patients. Results: In a cohort of 7 healthy controls and 9 patients with stage C or D HF, 7 miRNAs were differentially expressed. These miRNAs were further investigated in a second cohort of 80 patients with stage C or D HF and 30 healthy controls. Only miR-197-5P correlated with fibrosis as seen in cardiac magnetic resonance imaging in patients under the age of 50 years with stage C or D HF (r = 0.42, p = 0.008). Multivariate analyses revealed that miR-197-5P was also a risk factor for composite endpoint events in patients under the age of 50 years with stage C or D HF. Conclusion: miR-197-5P is a circulation miRNA that correlates with MF and adverse cardiac events in HF patients under the age of 50 years.

show abstract

Function and Therapeutic Potential of Noncoding RNAs in Cardiac Fibrosis

Cited by 98 publications

References 96 publications

Interleukin-10 Inhibits Bone Marrow Fibroblast Progenitor Cell–Mediated Cardiac Fibrosis in Pressure-Overloaded Myocardium

Interleukin-10 Inhibits Bone Marrow Fibroblast Progenitor Cell–Mediated Cardiac Fibrosis in Pressure-Overloaded Myocardium

Therapeutic potential of targeting microRNAs to regulate cardiac fibrosis: miR-433 a new fibrotic player

Association of miR-197-5p, a Circulating Biomarker for Heart Failure, with Myocardial Fibrosis and Adverse Cardiovascular Events among Patients with Stage C or D Heart Failure

Contact Info

Product

Resources

About