MicroRNA-451a attenuates angiotensin II–induced cardiac fibrosis and inflammation by directly targeting T-box1

Deng, Haoyuan; He, Ze-Yin; Dong, Zhi-Chao; Zhang, Yun-Long; Han, Xiao; Li, Huihua

doi:10.1007/s13105-021-00861-6

Cited by 11 publications

(10 citation statements)

References 41 publications

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“…A thorough systematic literature review was performed in search of experimental and/or clinical evidence of miRNAs (i) being involved in pathological cardiac remodeling in response to heart diseases or systemic cardio-metabolic alterations, (ii) holding a documented prognostic value for CV outcomes in at risk populations and (iii) possibly being involved in stress responses to acute or chronic kidney damage or in the cardio-renal axis. The results yielded pointed at miRNA 30a-5p [ 12–16 ], miRNA 23a-3p [ 17–20 ], miRNA 451a [ 21–26 ] and miRNA let7d-5p [ 16 , 27–31 ] as candidates for answering the opening research question. Under physiological conditions, all the four candidate miRNAs have previously been implicated in the development of various organs and tissues, including the heart, the kidney, the brain and the vascular system.…”

Section: Methodsmentioning

confidence: 99%

A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients

Bolignano

Greco

Presta

et al. 2023

Clinical Kidney Journal

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Background Chronic hemodialysis (HD) patients exhibit severe morpho-functional cardiac alterations, posing them at a high risk of death and adverse cardiovascular (CV) outcomes. Despite an unbalanced expression of various microRNAs (miRNAs) has been related to pathological cardiac remodelling and worse CV outcomes, scarce evidence exist on their role in this setting. Methods We evaluated circulating levels of a selected miRNAs panel (30a-5p, 23a-3p, 451a and let7d-5p) in 74 chronic HD patients together with a thorough clinical and echocardiography assessment. Individuals were then prospectly followed (median 22 mo.). The primary endpoint was a composite of all-cause and CV mortality and non-fatal CV events. Results Circulating levels of all miRNAs were lower in HD patients as compared to healthy controls and independently correlated to the severity of cardiac dysfunction. miRNA 30a-5p, 23a-3p and 451a expression was even lower in 30 subjects (40.5%) reaching the composite endpoint (p<0.001), while no differences were reported for let7d-5p. The predictive value of these miRNAs was supported by univariate followed by multivariate Cox-regression analyses (HR ranging from 0.943 to 0.995; p = 0.05 to 0.02) while Kaplan-Meier analyses confirmed a faster progression to the endpoint in individuals displaying miRNA levels below an optimal ROC-derived cut-off value (p ranging from 0.001 to <0.0001; crude HRs 7.95 to 8.61). Conclusions Lower circulating levels of miRNA 30-5p, 23a-3p and 451a in HD patients may reflect cardiac abnormalities and predict a higher risk of worse clinical outcomes in the short-mid term. Future studies on larger HD populations are needed to generalize these findings.

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Section: Methodsmentioning

confidence: 99%

A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients

Bolignano

Greco

Presta

et al. 2023

Clinical Kidney Journal

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“…A rat model has shown that miR-451a expression decreases in ischemia reperfusion injury, and up-regulation of miR-451a in myocardial tissue reduces the area of myocardial infarction, attenuates myocardial injury, and reduces myocardial cell apoptosis [33]. Human studies have shown that miR-451a expression is elevated in the plasma of patients with acute myocardial infarction compared with unstable coronary disease and healthy control groups [34], ánd that miR-451 has a regulatory role in ischemic heart injury [35]. The decreased miR-451a count in septic hearts compared with controls in the present study may support the assumption that myocardial dysfunction in sepsis is not caused by ischemia.…”

Section: Discussionmentioning

confidence: 99%

Postmortem analyses of myocardial microRNA expression in sepsis

Lehto,

Saukko,

Säkkinen

et al. 2024

Preprint

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Background Sepsis can lead to myocardial depression, playing a significant role in sepsis pathophysiology, clinical care, and outcome. To gain more insight into the pathophysiology of the myocardial response in sepsis, we investigated the expression of microRNA in myocardial autopsy specimens in critically ill deceased with sepsis and non-septic controls. Materials and methods In this retrospective observational study, we obtained myocardial tissue samples collected during autopsy from adult patients deceased with sepsis (n = 15) for routine histological examination. We obtained control myocardial tissue specimens (n = 15) from medicolegal autopsies of cadavers whose cause of death was injury or who were found dead at home and the cause of death was coronary artery disease with sudden cardiac arrest. RNA was isolated from formalin-fixed paraffin- embedded (FFPE) cardiac samples using the RecoverAll Total Nucleic Acid Isolation Kit for FFPE (Invitrogen). Differentially expressed miRNAs were identified using edgeR v3.32. MicroRNA was considered up- or down-regulated if the false discovery rate was < 0.05 and logarithmic fold change (log2FC) ≥ 1 for up-regulated or log2FC ≤ -1 for down-regulated miRNAs. The mean difference and 95% confidence interval (CI) was calculated for normalized read counts. Predicted miRNA targets were retrieved using Ingenuity Pathway Analysis (IPA) software, and pathway enrichment and classification were performed using PantherDB. Results Differential expression analysis identified a total of 32 miRNAs in the myocardial specimens. Eight miRNAs had a significant change in the mean difference based on the 95% CI, with the largest increase in mean counts in septic samples with hsa-miR-12136 and the highest fold change with hsa-miR-146b-5p. The threshold for down-regulated miRNAs in sepsis compared to controls was obtained with hsa-miR-144-5p and hsa-miR-451a, with the latter having the largest decrease in mean counts and fold decrease. Conclusions Several regulatory miRNAs were up- or down-regulated in the myocardial tissue of patients deceased with sepsis compared to non-septic subjects. The predicted target genes of miRNAs are associated with biological functions related to cardiovascular functions, cell viability, cell adhesion, and regulation of inflammatory and immune response.

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“…miR-451a expression is elevated in the plasma of patients with acute myocardial infarction (AMI) compared with unstable angina pectoris and healthy control groups [ 30 ]. Data suggest that miR-451a regulates ischemic heart injury [ 31 ]. Overexpression of miR-451a in mice significantly attenuated Ang II-induced cardiac fibrosis and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNA-451a and miRNA-328-3p as Potential Markers of Coronary Artery Aneurysmal Disease

Iwańczyk

Lehmann

Cieślewicz

et al. 2023

IJMS

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MicroRNAs (miRNAs) are currently investigated as crucial regulatory factors which may serve as a potential therapeutic target. Reports on the role of miRNA in patients with coronary artery aneurysmal disease (CAAD) are limited. The present analysis aims to confirm the differences in the expression of previously preselected miRNAs in larger study groups and evaluate their usefulness as potential markers of CAAD. The study cohort included 35 consecutive patients with CAAD (Group 1), and two groups of 35 patients matched Group 1 regarding sex and age from the overall cohort of 250 patients (Group 2 and Group 3). Group 2 included patients with angiographically documented coronary artery disease (CAD), while Group 3 enrolled patients with normal coronary arteries (NCA) assessed during coronary angiography. We applied the RT-qPCR method using the custom plates for the RT-qPCR array. We confirmed that the level of five preselected circulating miRNAs was different in patients with CAAD compared to Group 2 and Group 3. We found that miR-451a and miR-328 significantly improved the CAAD prediction. In conclusion, miR-451a is a significant marker of CAAD compared to patients with CAD. In turn, miR-328-3p is a significant marker of CAAD compared to patients with NCA.

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MicroRNA-451a attenuates angiotensin II–induced cardiac fibrosis and inflammation by directly targeting T-box1

Cited by 11 publications

References 41 publications

A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients

A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients

Postmortem analyses of myocardial microRNA expression in sepsis

Circulating miRNA-451a and miRNA-328-3p as Potential Markers of Coronary Artery Aneurysmal Disease

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