New Insights into the Functions of MicroRNAs in Cardiac Fibrosis: From Mechanisms to Therapeutic Strategies

Zhao, Yuanyuan; Du, Dunfeng; Chen, Shanshan; Chen, Zhishui; Zhao, Jiajia

doi:10.3390/genes13081390

Cited by 23 publications

(13 citation statements)

References 119 publications

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“…Since the discovery of miRNAs, interest in these molecules as potential diagnostic and therapeutic tools has grown [ 20 ]. There is plentiful evidence suggesting that miRNAs regulate cardiac homeostasis and thus may serve as a diagnostic tool and/or therapeutic target [ 21 ]. Several miRNAs targeting mRNA-encoding proteins involved in cardiac fibrosis are currently being assessed for their potential use as therapeutic targets, but these approaches are still at an early stage [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

miR-31-5p-Modified RAW 264.7 Macrophages Affect Profibrotic Phenotype of Lymphatic Endothelial Cells In Vitro

Moskalik

Ratajska

Majchrzak

et al. 2022

IJMS

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Cardiac lymphatic vessel (LyV) remodeling as a contributor to heart failure has not been extensively evaluated in metabolic syndrome (MetS). Our studies have shown structural changes in cardiac LyV in MetS that contribute to the development of edema and lead to myocardial fibrosis. Tissue macrophages may affect LyV via secretion of various substances, including noncoding RNAs. The aim of the study was to evaluate the influence of macrophages modified by miR-31-5p, a molecule that regulates fibrosis and lymphangiogenesis, on lymphatic endothelial cells (LECs) in vitro. The experiments were carried out on the RAW 264.7 macrophage cell line and primary dermal lymphatic endothelial cells. RAW 264.7 macrophages were transfected with miR-31-5p and supernatant from this culture was used for LEC stimulation. mRNA expression levels for genes associated with lymphangiogenesis and fibrosis were measured with qRT-PCR. Selected results were confirmed with ELISA or Western blotting. miR-31-5p-modified RAW 264.7 macrophages secreted increased amounts of VEGF-C and TGF-β and a decreased amount of IGF-1. The supernatant from miR-31-5p-modified RAW 264.7 downregulated the mRNA expression for genes regulating endothelial-to-mesenchymal transition (EndoMT) and fibrosis in LECs. Our results suggest that macrophages under the influence of miR-31-5p show the potential to inhibit LEC-dependent fibrosis. However, more studies are needed to confirm this effect in vivo.

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Section: Discussionmentioning

confidence: 99%

miR-31-5p-Modified RAW 264.7 Macrophages Affect Profibrotic Phenotype of Lymphatic Endothelial Cells In Vitro

Moskalik

Ratajska

Majchrzak

et al. 2022

IJMS

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“…Noteworthy, more than 60 non-coding microRNA (miRNA) have been reported to be involved in cardiac fibrosis. Many of these miRNAs modulate the TGFβ1 signaling pathway either directly by inhibiting TGFβ1, TGF β1 receptors, or smad proteins or indirectly by enhancing the TGFβ1/smad3 signaling pathway, thus conferring a pro- or anti-fibrotic property [ 48 ]. The exosome-mediated transport of miRNA was suggested to induce remote fibrotic effects besides many other cytokines and Wnt molecules.…”

Section: Molecular Mechanisms Involved In the Development Of Cardiac ...mentioning

confidence: 99%

“…Among them, the upregulation of circulating miR-21 and miR-133a was associated with cardiac fibrosis but in a non-specific manner. In the Eperelone Post-Acute Myocardial Infarction HF Efficacy and Survival Study (EPHESUS), only miR-113a was reported as a potentially specific circulating miRNA [ 48 , 128 ]. Thus, in the next few years, the development of standardized protocols for miRNA isolation and the correlation of miRNA with myocardial collagen content is necessary to consider miRNA as a circulating biomarker of cardiac fibrosis.…”

Section: Emerging Techniques For the Detection Of Cardiac Fibrosismentioning

confidence: 99%

Signaling Pathways and Potential Therapeutic Strategies in Cardiac Fibrosis

Bertaud

Joshkon

Heim

et al. 2023

IJMS

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Cardiac fibrosis constitutes irreversible necrosis of the heart muscle as a consequence of different acute (myocardial infarction) or chronic (diabetes, hypertension, …) diseases but also due to genetic alterations or aging. Currently, there is no curative treatment that is able to prevent or attenuate this phenomenon that leads to progressive cardiac dysfunction and life-threatening outcomes. This review summarizes the different targets identified and the new strategies proposed to fight cardiac fibrosis. Future directions, including the use of exosomes or nanoparticles, will also be discussed.

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“…miRNAs are broadly expressed in the nucleus and cytoplasm. However, miRNAs can still be found in blood circulation [ 101 ]. As miRNAs are expressed stably in blood, they are likely to be used as potential biomarkers for diagnostic, prognostic, and novel therapeutic strategies related to cardiovascular disease [ 102 ].…”

Section: Factors Influencing Cardiac Fibrosismentioning

confidence: 99%

Potential molecular mechanism underlying cardiac fibrosis in diabetes mellitus: a narrative review

et al. 2023

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Background Diabetes mellitus (DM) is among the most common risk factors for cardiovascular disease in the world with prevalence of more than 500 million population in 2021. Cardiac fibrosis with its complex process has been hypothesized as one of the mechanisms explaining development of heart failure in diabetic patients. Recently, the biomolecular mechanism of cardiac fibrosis in the hyperglycemia setting has been focusing around transforming growth factor β-1 (TGFβ-1) as a major factor. However, there is interplay role of several factors including microRNAs (miRNAs) which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1. In this review, we explored interplay role of several factors including microRNAs which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1 in diabetes mellitus. This narrative review included articles from the PubMed and Science Direct databases published in the last 10 years (2012–2022). Main text In diabetic patients, excessive activation of myofibroblasts occurs and triggers pro-collagen to convert into mature collagen to fill the cardiac interstitial space resulting in a pathological process of extracellular matrix remodeling. The balance between matrix metalloproteinase (MMP) and its inhibitor (tissue inhibitor of metalloproteinase, TIMP) is crucial in degradation of the extracellular matrix. Diabetes-related cardiac fibrosis is modulated by increasing level of TGF-β1 mediated by cellular components, including cardiomyocyte and non-cardiomyocyte cells involving fibroblasts, vascular pericytes smooth muscle cells, endothelial cells, mast cells, macrophages, and dendritic cells. Several miRNAs such as miR-21, miR-9, miR-29, miR-30d, miR-144, miR-34a, miR-150, miR-320, and miR-378 are upregulated in diabetic cardiomyopathy. TGF-β1, together with inflammatory cytokines, oxidative stress, combined sma and the mothers against decapentaplegic (smad) protein, mitogen-activated protein kinase (MAPK), and microRNAs, is interconnectedly involved in extracellular matrix production and fibrotic response. In this review, we explored interplay role of several factors including microRNAs which acts as a potential regulator of cardiac fibrosis connected with TGFβ-1 in diabetes mellitus. Conclusions Long-term hyperglycemia activates cardiac fibroblast via complex processes involving TGF-β1, miRNA, inflammatory chemokines, oxidative stress, smad, or MAPK pathways. There is increasing evidence of miRNA’s roles lately in modulating cardiac fibrosis.

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New Insights into the Functions of MicroRNAs in Cardiac Fibrosis: From Mechanisms to Therapeutic Strategies

Cited by 23 publications

References 119 publications

miR-31-5p-Modified RAW 264.7 Macrophages Affect Profibrotic Phenotype of Lymphatic Endothelial Cells In Vitro

miR-31-5p-Modified RAW 264.7 Macrophages Affect Profibrotic Phenotype of Lymphatic Endothelial Cells In Vitro

Signaling Pathways and Potential Therapeutic Strategies in Cardiac Fibrosis

Potential molecular mechanism underlying cardiac fibrosis in diabetes mellitus: a narrative review

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