• Biomarkers
• Diagnosis
• Hypertrophic cardiomyopathy
• MicroRNAs
• Pathogenesis
• Treatment

• Cardiomyopathy
• Epigenetic
• Hypertrophic cardiomyopathy
• Left ventricular hypertrophy
• Myocardium fibrosis
• microRNAs

• Biomarker
• Immune rejection
• Micro-RNAs
• Organ transplantation
• Tolerance
• Vascularized composite allotransplantations

• Biomarkers
• Graft Rejection/diagnosis
• Humans
• Immunosuppression Therapy
• MicroRNAs/genetics
• Vascularized Composite Allotransplantation

• atherosclerosis
• biomarker
• cardiovascular diseases
• epigenetics
• heart failure
• hypertension
• microRNA
• myocardial infarction

• YES proto-oncogene 1 (YES1)
• coronary heart disease (CHD)
• microRNA-140 (miR-140)
• mitochondria-mediated apoptosis
• myocardial ischemia-reperfusion (I/R) injury

Plasma microRNA (miR)-423-5p is a potential biomarker for the detection of colon cancer. However, the expression and biological role of miR-423-5p in colon tumorigenesis remains unclear. In the current study, reverse transcription-quantitative polymerase chain reaction was used to determine miR-423-5p expression in malignant colon tissues and plasma from patients with colon cancer. Cell viability, colony formation and apoptosis assays, as well as western blotting, were performed to investigate the biological role and regulatory mechanisms of miR-423-5p in colon cancer. The results demonstrated that miR-423-5p expression was downregulated in tumor tissues and plasma from patients with colon cancer, as well as in colon cancer cell lines. Furthermore, overexpression of miR-423-5p promoted colon cancer cell apoptosis and resulted in the inhibition of cell proliferation and colony formation. Mechanistically, miR-423-5p induced the expression of caspases 3, 8 and 9, as well as p53 in colon cancer. The effect of z-VAD treatment indicated that the miR-423-5p-mediated colon cancer cell apoptosis is caspase-dependent. These results suggest that miR-423-5p is a tumor suppressor in colon cancer and a potential diagnostic target to enable the early detection of colon cancer.

• apoptosis
• caspase
• colon cancer
• microRNA-423-5p

Previously, a number of microRNAs (miRs) have been identified to participate in the development and progression of glioma via the regulation of their target genes. However, the molecular mechanisms underlying the effect of miR-423-3p in glioma growth remain unclear. In the present study, the reverse transcription-quantitative polymerase chain reaction and western blotting were used to assess the mRNA and protein expression levels of miR-423-3p, respectively. An MTT assay and flow cytometry were performed to determine cell proliferation and apoptosis, respectively. A luciferase reporter gene assay was performed to determine the target association between pannexin 2 (PANX2) and miR-423-3p. It was revealed that miR-423-3p was significantly upregulated in glioma tissues compared with normal brain tissues, and the increased expression of miR-423-3p was significantly associated with an advanced grade as well as a poorer prognosis of patients with glioma. Inhibition of miR-423-3p using an miR-423-3p inhibitor resulted in the decreased proliferation of glioma U251 and U87MG Uppsala cells, and the induction of apoptosis. PANX2 was identified as a novel target gene of miR-423-3p, and the expression of PANX2 was revealed to be increased in U251 and U87MG Uppsala cells when miR-423-3p was inhibited. Knockdown of PANX2 attenuated the effects of miR-423-3p inhibition on glioma cell proliferation and apoptosis. Furthermore, PANX2 was significantly downregulated in glioma tissues compared with normal brain tissues, and its levels were markedly lower in World Health Organization (WHO) stage III–IV gliomas compared with WHO stage I–II gliomas. Additionally, the expression levels of PANX2 were identified to be inversely correlated with miR-423-3p expression levels in glioma tissues. Consequently, targeting miR-423-3p may inhibit glioma growth via the upregulation of PANX2.

• apoptosis
• glioma
• microRNA
• pannexin 2
• proliferation

• Circulating microRNA
• Coronary circulation
• Heart failure

• Circulating miRNA-195-3p
• Heart failure
• Next-generation sequencing

• Gerotarget
• circulating
• heart failure
• miRNA profile
• tissue

microRNAs (miRNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating miRNAs can be quantified in body liquids and are promising biomarkers in numerous diseases. In cardiovascular disease miRNAs have been proven to be reliable diagnostic biomarkers for different disease entities. In cardiac fibrosis (CF) and heart failure (HF) dysregulated circulating miRNAs have been identified, indicating their promising applicability as diagnostic biomarkers. Some miRNAs were successfully tested in risk stratification of HF implementing their potential use as prognostic biomarkers. In this respect miRNAs might soon be implemented in diagnostic clinical routine. In the young field of miRNA based research advances have been made in identifying miRNAs as potential targets for the treatment of experimental CF and HF. Promising study results suggest their potential future application as therapeutic agents in treatment of cardiovascular disease. This article summarizes the current state of the various aspects of miRNA research in the field of CF and HF with reduced ejection fraction as well as preserved ejection fraction. The review provides an overview of the application of circulating miRNAs as biomarkers in CF and HF and current approaches to therapeutically utilize miRNAs in this field of cardiovascular disease.

• MicroRNA
• Heart failure
• Cardiac fibrosis
• Biomarker
• Diagnostic
• Prognostic
• Heart failure with reduced ejection fraction
• Heart failure with preserved ejection fraction

• mirnas
• myomirs
• myocardial ischemia
• heart failure

• Apoptosis/physiology
• Feedback, Physiological/physiology
• Gene Expression Regulation/genetics
• Genetic Therapy/methods
• Humans
• MicroRNAs/genetics
• MicroRNAs/therapeutic use
• Myocardial Ischemia/genetics
• Myocardial Ischemia/physiopathology
• Myocardial Ischemia/therapy
• Myocytes, Cardiac/physiology
• Necrosis/physiopathology
• Neovascularization, Physiologic/physiology
• Regenerative Medicine/trends

• NFAT signaling
• circulating miRNA
• heart failure
• lncRNAs
• miRNA therapeutics
• microRNAs
• models, animal

The M₃ subtype of muscarinic acetylcholine receptors (M₃-mAChR) plays a protective role in myocardial ischemia and microRNAs (miRNAs) participate in many cardiac pathophysiological processes, including ischemia-induced cardiac injury. However, the role of miRNAs in M₃-mAChR mediated cardioprotection remains unexplored. The present study was designed to identify miRNAs that are involved in cardioprotective effects of M₃-mAChR against myocardial ischemia and elucidate the underlying mechanisms. We established rat model of myocardial ischemia and performed miRNA microarray analysis to identify miRNAs involved in the cardioprotection of M₃-mAChR. In H9c2 cells, the viability, intracellular free Ca²⁺ concentration ([Ca²⁺]i), intracellular reactive oxygen species (ROS), miR-376b-5p expression level, brain derived neurophic factor (BDNF) and nuclear factor kappa-B (NF-κB) levels were measured. Our results demonstrated that M₃-mAChR protected myocardial ischemia injury. Microarray analysis and qRT-PCR revealed that miR-376b-5p was significantly up-regulated in ischemic heart tissue and the M₃-mAChRs agonist choline reversed its up-regulation. In vitro, miR-376b-5p promoted H₂O₂-induced H9c2 cell injuries measured by cells viability, [Ca²⁺]i and ROS. Western blot and luciferase assay identified BDNF as a direct target of miR-376b-5p. M₃-mAChR activated NF-κB and thereby inhibited miR-376b-5p expression. Our data show that a novel M₃-mAChR/NF-κB/miR-376b-5p/BDNF axis plays an important role in modulating cardioprotection. MiR-376b-5p promotes myocardial ischemia injury possibly by inhibiting BDNF expression and M₃-mAChR provides cardioprotection at least partially mediated by the downregulation of miR-376b-5p through NF-κB. These findings provide new insight into the potential mechanism by which M₃-mAChR provides cardioprotection against myocardial ischemia injury.

• Animals
• Calcium/metabolism
• Cell Line
• Choline/pharmacology
• Down-Regulation
• Gene Expression Regulation
• Ischemia/pathology
• Male
• MicroRNAs/metabolism
• Models, Biological
• Myocardial Infarction/pathology
• Myocardial Ischemia/pathology
• Myocytes, Cardiac/pathology
• NF-kappa B/metabolism
• Rats
• Rats, Wistar
• Reactive Oxygen Species/metabolism
• Receptor, Muscarinic M3/genetics
• Receptor, Muscarinic M3/metabolism

Circulating microRNAs (miRNAs) have attracted major interest as biomarkers for cardiovascular diseases. Since RNases are abundant in circulating blood, there needs to be a mechanism protecting miRNAs from degradation. We hypothesized that microparticles (MP) represent protective transport vehicles for miRNAs and that these are specifically packaged by their maternal cells.

Conventional plasma preparations, such as the ones used for biomarker detection, are shown to contain substantial numbers of platelet-, leucocyte-, and endothelial cell-derived MP. To analyse the widest spectrum of miRNAs, Next Generation Sequencing was used to assess miRNA profiles of MP and their corresponding stimulated and non-stimulated cells of origin. THP-1 (monocytic origin) and human umbilical vein endothelial cell (HUVEC) MP were used for representing circulating MP at a high purity. miRNA profiles of MP differed significantly from those of stimulated and non-stimulated maternal THP-1 cells and HUVECs, respectively. Quantitative reverse transcription–polymerase chain reaction of miRNAs which have been associated with cardiovascular diseases also demonstrated significant differences in miRNA profiles between platelets and their MP. Notably, the main fraction of miRNA in plasma was localized in MP. Furthermore, miRNA profiles of MP differed significantly between patients with stable and unstable coronary artery disease.

Circulating MP represent transport vehicles for large numbers of specific miRNAs, which have been associated with cardiovascular diseases. miRNA profiles of MP are significantly different from their maternal cells, indicating an active mechanism of selective ‘packaging’ from cells into MP. These findings describe an interesting mechanism for transferring gene-regulatory function from MP-releasing cells to target cells via MP circulating in blood.

The recent discovery that microRNAs (miRNAs) are present in the circulation sparked interest in their use as potential biomarkers. In this review, we will summarize the latest findings on circulating miRNAs and cardiovascular disease but also discuss analytical challenges. While research on circulating miRNAs is still in its infancy, high analytical standards in statistics and study design are a prerequisite to obtain robust data and avoid repeating the mistakes of the early genetic association studies. Otherwise, studies tend to get published because of their novelty despite low numbers, poorly matched cases and controls and no multivariate adjustment for conventional risk factors. Research on circulating miRNAs can only progress by bringing more statistical rigour to bear in this field and by evaluating changes of individual miRNAs in the context of the overall miRNA network. Such miRNA signatures may have better diagnostic and prognostic value.

• mirna expression profile
• heart
• translational repression or activation
• stability of microrna

• Animals
• Humans
• MicroRNAs/biosynthesis
• Myocardial Ischemia/drug therapy
• Myocardial Ischemia/metabolism
• Myocardial Ischemia/physiopathology
• Resveratrol
• Stilbenes/metabolism
• Stilbenes/therapeutic use

• Z99 AA999999 Intramural NIH HHS
• R01 HL034360 NHLBI NIH HHS
• HL 34360 NHLBI NIH HHS
• R01 HL022559 NHLBI NIH HHS
• HL22559 NHLBI NIH HHS
• HL 33889 NHLBI NIH HHS