MicroRNAs as mediators of cardiovascular disease: Targets to be manipulated

Lee, Seahyoung; Choi, Eun Kyoung; Kim, Sung-Man; Hwang, Ki‐Chul

doi:10.4331/wjbc.v6.i2.34

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…It has been argued that non-physiological expression of miRNAs may contribute to both development and progression of cardiovascular diseases 40 . As demonstrated in rats, heart and lungs are the organs where the highest levels of bulky DNA adducts are detectable following exposure to ECS, and these nucleotide alterations are more persistent in the heart, presumably because of the less efficient DNA repair capacities in this organ 14 .…”

Section: Discussionmentioning

confidence: 99%

Release of MicroRNAs into Body Fluids from Ten Organs of Mice Exposed to Cigarette Smoke

Izzotti¹,

Longobardi²,

Maestra³

et al. 2018

Theranostics

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Purpose: MicroRNAs are small non-coding RNAs that regulate gene expression, thereby playing a role in a variety of physiological and pathophysiological states. Exposure to cigarette smoke extensively downregulates microRNA expression in pulmonary cells of mice, rats, and humans. Cellular microRNAs are released into body fluids, but a poor parallelism was previously observed between lung microRNAs and circulating microRNAs. The purpose of the present study was to validate the application of this epigenetic biomarker by using less invasive collection procedures.Experimental design: Using microarray analyses, we measured 1135 microRNAs in 10 organs and 3 body fluids of mice that were either unexposed or exposed to mainstream cigarette smoke for up to 8 weeks. The results obtained with selected miRNAs were validated by qPCR.Results: The lung was the main target affected by smoke (190 dysregulated miRNAs), followed by skeletal muscle (180), liver (138), blood serum (109), kidney (96), spleen (89), stomach (36), heart (33), bronchoalveolar lavage fluid (32), urine (27), urinary bladder (12), colon (5), and brain (0). Skeletal muscle, kidney, and lung were the most important sources of smoke-altered microRNAs in blood serum, urine, and bronchoalveolar lavage fluid, respectively.Conclusions: microRNA expression analysis was able to identify target organs after just 8 weeks of exposure to smoke, well before the occurrence of any detectable histopathological alteration. The present translational study validates the use of body fluid microRNAs as biomarkers applicable to human biomonitoring for mechanistic studies, diagnostic purposes, preventive medicine, and therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Release of MicroRNAs into Body Fluids from Ten Organs of Mice Exposed to Cigarette Smoke

Izzotti¹,

Longobardi²,

Maestra³

et al. 2018

Theranostics

View full text Add to dashboard Cite

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“…Several studies impart information establishing miRNAs as key regulators of cardiovascular diseases [14,15]. Interestingly, few reports have proposed the diagnostic potential of miRNAs in cardiac complications such as MI [16] and heart failure [17].…”

Section: Introductionmentioning

confidence: 99%

Circulatory miR-133b and miR-21 as Novel Biomarkers in Early Prediction and Diagnosis of Coronary Artery Disease

Kumar

Narang

Sreenivas

et al. 2020

Genes

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While coronary artery disease (CAD) has become a major threat worldwide, the timely biomarker-based early diagnosis of CAD remains a major unmet clinical challenge. We aimed towards assessing the level of circulatory microRNAs as candidates of novel biomarkers in patients with CAD. A total of 147 subjects were recruited which includes 78 subjects with angiographically proven CAD, 15 pre-atherosclerotic normal coronary artery (NCA) subjects and 54 healthy individuals. Quantitative real-time PCR assays were performed. MiR-133b was downregulated by 4.6 fold (p < 0.0001) whereas miR-21 was upregulated by ~2 fold (p < 0.0001) in plasma samples of CAD patients. Importantly, both the miRNAs showed association with disease severity as miR-133b was downregulated by 8.45 fold in acute coronary syndrome (ACS), 3.38 fold in Stable angina (SA) and 2.08 fold in NCA. MiR-21 was upregulated by 2.46 fold in ACS, 1.90 fold in SA and 1.12 fold in NCA. Moreover, miR-133b could significantly differentiate subjects with ST-elevation myocardial infarction (STEMI) from Non-STEMI. Area under the curve (AUC) for miR-133b was 0.80 with >75.6% sensitivity and specificity, AUC for miR-21 was 0.79 with >69.4% sensitivity and specificity. Our results suggest that miR-133b and miR-21 could be possible candidates of novel biomarkers in early prediction of CAD.

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“…In addition, EVs act as an extracellular reservoir that releases specific molecules with different spatial and temporal distribution profiles compared to whole cells. The miR-dependent regulation of cell signaling acts like an ID card that directs the production of trophic factors, such as proteins and growth factors to improve various diseases 47 , 48 . We named the common role of miRs and EVs a “multiplexed target”.…”

Section: Discussionmentioning

confidence: 99%

Multiplexed targeting of miRNA-210 in stem cell-derived extracellular vesicles promotes selective regeneration in ischemic hearts

et al. 2021

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Extracellular vesicles (EVs) are cell derivatives containing diverse cellular molecules, have various physiological properties and are also present in stem cells used for regenerative therapy. We selected a “multiplexed target” that demonstrates multiple effects on various cardiovascular cells, while functioning as a cargo of EVs. We screened various microRNAs (miRs) and identified miR-210 as a candidate target for survival and angiogenic function. We confirmed the cellular and biological functions of EV-210 (EVs derived from ASCmiR-210) secreted from adipose-derived stem cells (ASCs) transfected with miR-210 (ASCmiR-210). Under hypoxic conditions, we observed that ASCmiR-210 inhibits apoptosis by modulating protein tyrosine phosphatase 1B (PTP1B) and death-associated protein kinase 1 (DAPK1). In hypoxic endothelial cells, EV-210 exerted its angiogenic capacity by inhibiting Ephrin A (EFNA3). Furthermore, EV-210 enhanced cell survival under the control of PTP1B and induced antiapoptotic effects in hypoxic H9c2 cells. In cardiac fibroblasts, the fibrotic ratio was reduced after exposure to EV-210, but EVs derived from ASCmiR-210 did not communicate with fibroblasts. Finally, we observed the functional restoration of the ischemia/reperfusion-injured heart by maintaining the intercommunication of EVs and cardiovascular cells derived from ASCmiR-210. These results suggest that the multiplexed target with ASCmiR-210 is a useful tool for cardiovascular regeneration.

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MicroRNAs as mediators of cardiovascular disease: Targets to be manipulated

Cited by 7 publications

References 39 publications

Release of MicroRNAs into Body Fluids from Ten Organs of Mice Exposed to Cigarette Smoke

Release of MicroRNAs into Body Fluids from Ten Organs of Mice Exposed to Cigarette Smoke

Circulatory miR-133b and miR-21 as Novel Biomarkers in Early Prediction and Diagnosis of Coronary Artery Disease

Multiplexed targeting of miRNA-210 in stem cell-derived extracellular vesicles promotes selective regeneration in ischemic hearts

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