AntimiR-21 Prevents Myocardial Dysfunction in a Pig Model of Ischemia/Reperfusion Injury

Hinkel, Rabea; Ramanujam, Deepak; Kaczmarek, Veronika; Howe, Andrea; Klett, Katharina; Beck, Christina M.; Dueck, Anne; Thum, Thomas; Laugwitz, Karl‐Ludwig; Maegdefessel, Lars; Weber, Christian; Kupatt, Christian; Engelhardt, Stefan

doi:10.1016/j.jacc.2020.02.041

Cited by 110 publications

(84 citation statements)

References 25 publications

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“…As a limitation, our study could have benefitted from additional time points, as there is some evidence of altering functions of miRNAs in tissues depending on the time point, as previously mentioned [42]. The proportion of patients whose cardiac index was measured was fairly small in this study.…”

Section: Discussionmentioning

confidence: 87%

Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock

Hänninen

Jäntti

Tolppanen

et al. 2020

IJMS

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Cardiogenic shock (CS) is a life-threatening emergency. New biomarkers are needed in order to detect patients at greater risk of adverse outcome. Our aim was to assess the characteristics of miR-21-5p, miR-122-5p, and miR-320a-3p in CS and evaluate the value of their expression levels in risk prediction. Circulating levels of miR-21-5p, miR-122-5p, and miR-320a-3p were measured from serial plasma samples of 179 patients during the first 5–10 days after detection of CS, derived from the CardShock study. Acute coronary syndrome was the most common cause (80%) of CS. Baseline (0 h) levels of miR-21-5p, miR-122-5p, and miR-320a-3p were all significantly elevated in nonsurvivors compared to survivors (p < 0.05 for all). Above median levels at 0h of each miRNA were each significantly associated with higher lactate and alanine aminotransferase levels and decreased glomerular filtration rates. After adjusting the multivariate regression analysis with established CS risk factors, miR-21-5p and miR-320a-3p levels above median at 0 h were independently associated with 90-day all-cause mortality (adjusted hazard ratio 1.8 (95% confidence interval 1.1–3.0), p = 0.018; adjusted hazard ratio 1.9 (95% confidence interval 1.2–3.2), p = 0.009, respectively). In conclusion, circulating plasma levels of miR-21-5p, miR-122-5p, and miR-320a-3p at baseline were all elevated in nonsurvivors of CS and associated with markers of hypoperfusion. Above median levels of miR-21-5p and miR-320a-3p at baseline appear to independently predict 90-day all-cause mortality. This indicates the potential of miRNAs as biomarkers for risk assessment in cardiogenic shock.

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Section: Discussionmentioning

confidence: 87%

Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock

Hänninen

Jäntti

Tolppanen

et al. 2020

IJMS

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“…102 A validation study was done in large animals after MI. 103 Kidney Disease miR-21. In the context of kidney diseases, miR-21 was also found to be enriched in the kidney.…”

Section: Toxicity Of Asosmentioning

confidence: 99%

Pharmacokinetics and Proceedings in Clinical Application of Nucleic Acid Therapeutics

Herkt

Thum

2021

Molecular Therapy

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“…Nevertheless, some studies also showed that miR-21 is a cardio-and reno-protective miRNA in acute disease states, such as acute myocardial infarction. Based on the association and promising preclinical data for antisense oligonucleotide (ASO)-mediated targeting of miR-21 in the heart and kidneys (Thum et al, 2008;Zhong et al, 2011;Liang et al, 2012;Wang et al, 2013;Chuppa et al, 2018;Hinkel et al, 2020), (Dong et al, 2009;Cheng et al, 2010;Corsten et al, 2010;Lorenzen et al, 2013;Vegter et al, 2016;Yang et al, 2018) 2 Chronic heart failure Chronic kidney disease miR-21, miR-22, miR-133 (Care et al, 2007;Zawada et al, 2014;Zhang et al, 2016) 3 Acute kidney injury Cardiovascular disease miR-21, miR-20a, miR-24 (Thum et al, 2008;Godwin et al, 2010;Lorenzen et al, 2014;Vegter et al, 2016) 4 Chronic kidney disease Chronic heart failure miR-21, miR-155, miR-29 (Lv et al, 2013;Gaede et al, 2016;Chuppa et al, 2018) 5 Systemic disease (sepsis, DM, SLE … etc)…”

Section: Mirnas and Their Role In Cardiorenal Syndromementioning

confidence: 99%

“…Similar to its role in heart disease, miR-21 contributes to the progression of acute and chronic stages in kidney disease and also has distinct roles in early and late disease stage (Hinkel et al, 2020). In some studies, AKI induced by ischemia reperfusion injury (IRI), activates massive inflammation, epithelial cell apoptosis, and fibrosis (Brandenburger et al, 2018).…”

Section: Mir-21 In Kidney Diseasementioning

confidence: 99%

miR-21, Mediator, and Potential Therapeutic Target in the Cardiorenal Syndrome

2020

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Oligonucleotide-based therapies are currently gaining attention as a new treatment option for relatively rare as well as common diseases such as cardiovascular disease. With the remarkable progression of new sequencing technologies, a further step towards personalized precision medicine to target a disease at a molecular level was taken. Such therapies may employ antisense oligonucleotides to modulate the expression of both protein coding and non-coding RNAs, such as microRNAs. The cardiorenal syndrome (CRS) is a complex and severe clinical condition where heart and renal dysfunction mutually affect one another. The underlying mechanisms remain largely unknown and current treatments of CRS are mainly supportive therapies which slow down the progression of the disease, but hardly improve the condition. The small noncoding RNA, microRNA-21 (miR-21), is dysregulated in various heart and kidney diseases and has been repeatedly suggested as therapeutic target for the treatment of CRS. Impressive preclinical results have been achieved by an antisense oligonucleotide-based therapy to effectively block the pro-fibrotic traits of miR-21. Since microRNA-mediated pathways are generally very well-conserved, there is considerable commercial interest with regards to clinical translation. In this review, we will summarize the role of miR-21 within the heart-kidney axis and discuss the advantages and pitfalls of miR-21 targeting therapeutic strategies in CRS.

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AntimiR-21 Prevents Myocardial Dysfunction in a Pig Model of Ischemia/Reperfusion Injury

Cited by 110 publications

References 25 publications

Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock

Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock

Pharmacokinetics and Proceedings in Clinical Application of Nucleic Acid Therapeutics

miR-21, Mediator, and Potential Therapeutic Target in the Cardiorenal Syndrome

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