Genetic Dissection of the Impact of miR-33a and miR-33b during the Progression of Atherosclerosis

Cell Reports, Journal Year: 2017, Volume and Issue: 21(5), P. 1317 - 1330

Published: Oct. 1, 2017

As an important regulator of macrophage cholesterol efflux and HDL biogenesis, miR-33 is a promising target for treatment atherosclerosis, numerous studies demonstrate that inhibition increases levels reduces plaque burden. However, questions remain about how impacts atherogenesis, including whether this protection primarily due to direct effects on macrophages or regulation lipid metabolism in the liver. We deficiency Ldlr-/- mice promotes obesity, insulin resistance, hyperlipidemia but does not impact development. further assess loss addition miR-33b other hematopoietic cells atherogenesis. Macrophage-specific decreases accumulation inflammation under hyperlipidemic conditions, leading reduced Therefore, pro-atherogenic observed miR-33-deficient are likely counterbalanced by protective macrophages, which may be primary mechanism through anti-miR-33 therapies reduce atherosclerosis.

Language: Английский

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Biology of Tissue Inhibitor of Metalloproteinase 3 (TIMP3), and Its Therapeutic Implications in Cardiovascular Pathology

Frontiers in Physiology, Journal Year: 2020, Volume and Issue: 11

Published: June 16, 2020

Tissue inhibitor of metalloproteinase 3 (TIMP3) is unique among the four TIMPs due to its extracellular matrix (ECM)-binding property and broad range inhibitory substrates that includes metalloproteinases (MMPs), a disintegrin (ADAMs), ADAM with thrombospondin motifs (ADAMTSs). In addition metalloproteinase-inhibitory function, TIMP3 can interact proteins in space resulting multifarious functions. mRNA has long 3' untranslated region (UTR) which target for numerous microRNAs. levels are reduced various cardiovascular diseases, studies have shown replenishment ameliorates disease, suggesting therapeutic potential diseases. While significant efforts been made identifying effector targets TIMP3, regulatory mechanism expression this multi-functional TIMP less explored. Here, we provide an overview gene structure, transcriptional post-transcriptional regulators (transcription factors microRNAs), protein structure partners, role pathology application as therapy, while also drawing reference from function other

Language: Английский

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LncRNA 2810403D21Rik/Mirf promotes ischemic myocardial injury by regulating autophagy through targeting Mir26a

Autophagy, Journal Year: 2019, Volume and Issue: 16(6), P. 1077 - 1091

Published: Sept. 12, 2019

More evidence is emerging of the roles long non-coding RNAs (lncRNAs) play as regulatory factors in a variety biological processes, but mechanisms underlying function lncRNAs acute myocardial infarction (AMI) have not been explicitly delineated. The present study identified lncRNA 2810403D21Rik/AK007586/Mirf (myocardial infarction-regulatory factor), that inhibited macroautophagy/autophagy by modulating Mir26a (microRNA 26a). Inhibition led to cardiac injury both vitro and vivo, whereas overexpression attenuated ischemic stress-induced cell death activating autophagy through targeting Usp15 (ubiquitin specific peptidase 15). importantly, 2810403D21Rik/Mirf acted competitive endogenous RNA (ceRNA) Mir26a; forced expression downregulated inhibit autophagy. In contrast, loss resulted upregulation promote alleviate injury, which turn improved MI mice. This functions an anti-autophagic molecule via ceRNA activity toward Mir26a. Our findings suggest knockdown might be novel therapeutic approach for diseases associated with autophagy.Abbreviations 3-MA: 3-methyladenine; AAV-9: adenovirus virus-9; agoMir26a: cholesterol-conjugated mimic; AMI: infarction; AMO-26a: inhibitor; ATG: related; BECN1: beclin 1; ceRNA: RNAs; EF: ejection fraction; f-2810403D21Rik/Mirf: fragment encompassing binding site; FS: fraction shortening; GFP-mRFP: plasmid expressing green fluorescent protein-monomeric red protein; lncRNA: RNA; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; Mirf: factor; miRNAs: microRNAs; NC: negative control; NMCMs: neonatal mice cardiomyocytes; shRNA: short hairpin siRNA: small interfering SQSTM1/p62: sequestosome TEM: transmission electron microscopy; Usp15: ubiquitin 15.

Language: Английский

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Circulating miR-122-5p/miR-133b Ratio Is a Specific Early Prognostic Biomarker in Acute Myocardial Infarction

Circulation Journal, Journal Year: 2016, Volume and Issue: 80(10), P. 2183 - 2191

Published: Jan. 1, 2016

MicroRNAs (miRNAs) are key players in cardiovascular development and disease. However, not only miRNAs of a cardiac origin have critical role heart function. Recent studies demonstrated that miR-122-5p, hepatic miRNA, increases the bloodstream during ischemic cardiogenic shock it is upregulated infarcted myocardium. The aim present study was to determine potential circulating miR-122-5p as biomarker for early prognostic stratification ST-segment elevation acute myocardial infarction (STEMI) patients.One hundred forty-two consecutive STEMI patients treated with primary angioplasty were included study. Serum levels miR-1-3p, -122-5p, -133a-3p, -133b, -208b-3p -499a-5p measured at time catheterization by quantitative polymerase chain reaction related in-hospital long-term outcome. During follow up 20.8 months, 9 died, 6 had recurrence infarction, 26 suffered an adverse event. Event-free survival significantly worse higher miR-122-5p/133b ratio (3rd tertile distribution, above 1.42 Log(10)), having almost 9-fold risk death or 4-fold events.This showed new identification developing major events after undergoing percutaneous coronary intervention. (Circ J 2016; 80: 2183-2191).

Language: Английский

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Non-coding RNAs as biomarkers for acute myocardial infarction

Acta Pharmacologica Sinica, Journal Year: 2018, Volume and Issue: 39(7), P. 1110 - 1119

Published: April 26, 2018

Language: Английский

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