MicroRNAs in Inflammatory Heart Diseases and Sepsis-Induced Cardiac Dysfunction: A Potential Scope for the Future?

Mirna, Moritz; Paar, Vera; Rezar, Richard; Topf, Albert; Eber, M; Hoppe, Uta C.; Lichtenauer, Michael; Jung, Christian

doi:10.3390/cells8111352

Cited by 53 publications

(35 citation statements)

References 75 publications

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“…Recent findings suggest a key role for noncoding RNAs, especially circRNA and microRNAs (miRNAs), in the progression and management of the inflammatory response through the stability and maintenance of gene expression (25,26). Several miRNAs, such as miR-124, miR-30a, and miR-193a-5p, have emerged as important transcriptional regulators of some inflammatory mediators (27,28).…”

Section: Discussionmentioning

confidence: 99%

CircHIPK3 Promotes Pyroptosis in Acinar Cells Through Regulation of the miR-193a-5p/GSDMD Axis

Wang

Liu

et al. 2020

Front. Med.

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Acute pancreatitis (AP), especially severe acute pancreatitis (SAP), is an extremely dangerous illness with a high mortality rate. Pyroptotic cells release their cellular contents and inflammatory factors, aggravating the inflammatory response. Pyroptosis may be the main mode of acinar cell death during AP. The circular RNA circHIPK3 is expressed in pancreatic tissue and is associated with inflammatory response. In this study, we focused on the role and underlying mechanism of circHIPK3 in AP. We found that the expression of circHIPK3 was significantly elevated in serum of patients with AP and in caerulein-stimulated AR42J cells and was associated with caspase-1 and caspase-11 activation. circHIPK3 silencing ameliorated caerulein-induced cell damage and reduced the release of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α and inhibited the activation of caspase-1 and caspase-11. In addition, circHIPK3 bound to miR-193a-5p and negatively regulated its expression. Inhibition of miR-193a-5p increased the release of IL-1β, IL-6, IL-8, and TNF-α and activated caspase-1 and caspase-11, thereby counteracting the effect of circHIPK3 silencing on caerulein-induced cell damage. Furthermore, we identified GSDMD as a target gene of miR-193a-5p, which is the key gene for pyroptosis. Interfering with the expression of GSDMD can increase cell viability, reduce the secretion of inflammatory cytokines, and suppress the activation of cleaved caspase-1 and caspase-11. Silencing GSDMD reversed the effects of miR-193a-5p inhibitors on caerulein-induced damage. In conclusion, circHIPK3 promotes pyroptosis in acinar cells through regulation of the miR-193a-5p/GSDMD axis, which eventually aggravates AP disease.

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Section: Discussionmentioning

confidence: 99%

CircHIPK3 Promotes Pyroptosis in Acinar Cells Through Regulation of the miR-193a-5p/GSDMD Axis

Wang

Liu

et al. 2020

Front. Med.

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“…After enzymatic processing, the mature miRNA binds to RNA-induced silencing complexes (RISC), which then binds complementary messenger RNAs (mRNAs), thusly preventing protein synthesis (84,85). MiRNAs can be found in all eukaryotic organisms and are probably involved in the regulation of a wide variety of physiologic and pathophysiologic processes (86). In fact, recent studies suggest that a variety of miRNAs play a role in pathophysiologic processes involved in the development and progression of heart failure (HF), such as cardiac remodeling, inflammation or myocardial fibrosis (87)(88)(89).…”

Section: Micrornas In Heart Failure (Hf)mentioning

confidence: 99%

The Diagnostic and Therapeutic Value of Multimarker Analysis in Heart Failure. An Approach to Biomarker-Targeted Therapy

Topf

Mirna

Ohnewein

et al. 2020

Front. Cardiovasc. Med.

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Background: Heart failure is a pathophysiological state, which is still associated with high morbidity and mortality despite established therapies. Diverse well-known biomarkers fail to assess the variety of individual pathophysiology in the context of heart failure.Methods: An analysis of prospective, multimarker-specific therapeutic approaches to heart failure based on studies in current literature was performed. A total of 159 screened publications in the field of biomarkers in heart failure were hand-selected and found to be eligible for this study by a team of experts.Results: Established biomarkers of the inflammatory axis, matrix remodeling, fibrosis and oxidative stress axis, as well as potential therapeutic interventions were investigated. Interaction with end organs, such as cardio-hepatic, cardio-renal and cardio-gastrointestinal interactions show the complexity of the syndrome and could be of further therapeutic value. MicroRNAs are involved in a wide variety of physiologic and pathophysiologic processes in heart failure and could be useful in diagnostic as well as therapeutic setting.Conclusion: Based on our analysis by a biomarker-driven approach in heart failure therapy, patients could be treated more specifically in long term with a consideration of different aspects of heart failure. New studies evaluating a multimarker – based therapeutic approach could lead in a decrease in the morbidity and mortality of heart failure patients.

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“…Non-coding RNAs regulate gene expression by binding to complementary regions of transcripts to inhibit their translation and/or promote messenger RNA (mRNA) degradation, thereby regulating biological processes including vertebrate development (for a review, see References [44][45][46][47]). In particular, microRNAs (miRNAs or miRs) regulate heart development and functional physiologic processes.…”

Section: Non-coding Rnas and Cardiotoxicitymentioning

confidence: 99%

“…More recently, miRNAs were recognized to play important roles in HF, and they are involved in several pathophysiological processes related to HF [45][46][47]. Moreover, specific miRNAs are also identified in blood circulation and may be used as potential diagnostic and prognostic biomarkers for HF [65].…”

Section: Is It Possible To Identify Common Factors Playing a Role In mentioning

confidence: 99%

Cardiotoxicity and Heart Failure: Lessons from Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Anticancer Drugs

Sachinidis

2020

Cells

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Human-induced pluripotent stem cells (hiPSCs) are discussed as disease modeling for optimization and adaptation of therapy to each individual. However, the fundamental question is still under debate whether stem-cell-based disease modeling and drug discovery are applicable for recapitulating pathological processes under in vivo conditions. Drug treatment and exposure to different chemicals and environmental factors can initiate diseases due to toxicity effects in humans. It is well documented that drug-induced cardiotoxicity accelerates the development of heart failure (HF). Until now, investigations on the understanding of mechanisms involved in HF by anticancer drugs are hindered by limitations of the available cellular models which are relevant for human physiology and by the fact that the clinical manifestation of HF often occurs several years after its initiation. Recently, we identified similar genomic biomarkers as observed by HF after short treatment of hiPSCs-derived cardiomyocytes (hiPSC-CMs) with different antitumor drugs such as anthracyclines and etoposide (ETP). Moreover, we identified common cardiotoxic biological processes and signal transduction pathways which are discussed as being crucial for the survival and function of cardiomyocytes and, therefore, for the development of HF. In the present review, I discuss the applicability of the in vitro cardiotoxicity test systems as modeling for discovering preventive mechanisms/targets against cardiotoxicity and, therefore, for novel HF therapeutic concepts.

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MicroRNAs in Inflammatory Heart Diseases and Sepsis-Induced Cardiac Dysfunction: A Potential Scope for the Future?

Cited by 53 publications

References 75 publications

CircHIPK3 Promotes Pyroptosis in Acinar Cells Through Regulation of the miR-193a-5p/GSDMD Axis

CircHIPK3 Promotes Pyroptosis in Acinar Cells Through Regulation of the miR-193a-5p/GSDMD Axis

The Diagnostic and Therapeutic Value of Multimarker Analysis in Heart Failure. An Approach to Biomarker-Targeted Therapy

Cardiotoxicity and Heart Failure: Lessons from Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Anticancer Drugs

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