Circulating MicroRNAs as Novel Biomarkers of Stenosis Progression in Asymptomatic Carotid Stenosis

Dolz, Sandra; Górriz, David; Tembl, José Ignacio; Sanchez, Dolors; Fortea, Gerardo; Parkhutik, Vera; Lago, Aída

doi:10.1161/strokeaha.116.013650

Cited by 80 publications

(62 citation statements)

References 32 publications

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“…Other studies have previously found these miRNAs to be increased in the blood during other pathological conditions as well [28,34]. Other studies have previously found these miRNAs to be increased in the blood during other pathological conditions as well [28,34].…”

Section: Discussionmentioning

confidence: 92%

Extracellular microRNA 130b‐3p inhibits eCIRP‐induced inflammation

et al. 2019

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Although microRNAs regulate mRNA expression intracellularly, they are often released into the circulation in inflammatory diseases. During sepsis, secreted extracellular cold-inducible RNAbinding protein (eCIRP) acts as a damage-associated molecular pattern (DAMP), inducing tissue damage by elevating inflammatory cytokines and chemokines. Here, we report that the circulating microRNA 130b-3p inhibits eCIRP-mediated sterile and cecal ligation and puncture (CLP)-induced non-sterile inflammation. We find that levels of miR-130b-3p are increased in the serum of septic mice and patients and that it strongly interacts with recombinant murine (rm) CIRP in vitro and with eCIRP in the serum of septic mice in vivo. Combining a miR-130b-3p mimic with rmCIRP significantly decreases TNF-a release by macrophages compared to only rmCIRP-treated cells. This combined treatment also dose-dependently decreases the affinity of rmCIRP with its receptor TLR4/ MD2. Finally, injection of a miR-130b-3p mimic significantly reduces rmCIRP-or CLP-induced systemic inflammation and acute lung injury in mice. These data show that extracellular miR-130b-3p functions as a novel endogenous inhibitor of eCIRP and point to an innovative therapeutic approach to treat inflammatory diseases.

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Section: Discussionmentioning

confidence: 92%

Extracellular microRNA 130b‐3p inhibits eCIRP‐induced inflammation

et al. 2019

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“…Asymptomatic carotid stenosis [63], familial hypercholesterolemia and coronary artery disease [64], angina pectoris [65], ischemic dilated cardiomyopathy [66], small and large abdominal aortic aneurysm [61], myocardial ischemia/reperfusion [67,68], diabetes mellitus [14,24,52,54] hsa-miR-26a-5p 3p22.2 12q14.1 [69] Heart failure, cardiac hypertrophy [70], myocardial infarction [51,71,72], ischemia/reperfusion injury [73], pulmonary arterial hypertension [74], T1DM [75], diabetic nephropathy [57] hsa-miR-29a-3p 7q32.3…”

Section: Introductionmentioning

confidence: 99%

“…Asymptomatic carotid stenosis [63], cardiac amyloidosis [150], heart failure [151], atherosclerosis [152,153], aortic stenosis [154], acute myocardial infarction [155], acute ischemic stroke [156], focal cerebral ischemia [157], pulmonary artery hypertension [158], obesity [159] hsa-miR-342-3p 14q32.2 Cardiac amyloidosis [150], obesity [160], T1DM [52,149,161], T2DM [149,162,163], GDM [149], endothelial dysfunction [164] hsa-miR-499a-5p 20q11. 22 Myocardial infarction [17,165], hypoxia [166], cardiac regeneration [167], vascular endothelial dysfunction [15] hsa-miR-574-3p 4p14 Myocardial infarction [168], coronary artery disease [100], cardiac amyloidosis [150], stroke [169], T2DM [104,170]…”

Section: Introductionmentioning

confidence: 99%

Diabetes Mellitus and Cardiovascular Risk Assessment in Mothers with a History of Gestational Diabetes Mellitus Based on Postpartal Expression Profile of MicroRNAs Associated with Diabetes Mellitus and Cardiovascular and Cerebrovascular Diseases

Hromadníková

Dvořáková

Krofta

2020

IJMS

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Mothers with a history of gestational diabetes mellitus (GDM) have an increased risk of developing diabetes in the future and a lifelong cardiovascular risk. Postpartal expression profile of cardiovascular/cerebrovascular disease associated microRNAs was assessed 3–11 years after the delivery in whole peripheral blood of young and middle-aged mothers with a prior exposure to GDM with the aim to identify a high-risk group of mothers at risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases who would benefit from implementation of early primary prevention strategies and long-term follow-up. The hypothesis of the assessment of cardiovascular risk in women was based on the knowledge that a series of microRNAs play a role in the pathogenesis of diabetes mellitus and cardiovascular/cerebrovascular diseases. Abnormal expression profile of multiple microRNAs was found in women with a prior exposure to GDM (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and-miR-574-3p). Postpartal combined screening of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p showed the highest accuracy for the identification of mothers with a prior exposure to GDM at a higher risk of later development of cardiovascular/cerebrovascular diseases (AUC 0.900, p < 0.001, sensitivity 77.48%, specificity 93.26%, cut off >0.611270413). It was able to identify 77.48% mothers with an increased cardiovascular risk at 10.0% FPR. Any of changes in epigenome (upregulation of miR-16-5p, miR-17-5p, miR-29a-3p, and miR-195-5p) that were induced by GDM-complicated pregnancy are long-acting and may predispose mothers affected with GDM to later development of diabetes mellitus and cardiovascular/cerebrovascular diseases. In addition, novel epigenetic changes (upregulation of serious of microRNAs) appeared in a proportion of women that were exposed to GDM throughout the postpartal life. Likewise, a previous occurrence of either GH, PE, and/or FGR, as well as a previous occurrence of GDM, is associated with the upregulation of miR-1-3p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-29a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p. On the other hand, upregulation of miR-16-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-103a-3p, miR-195-5p, miR-342-3p, and miR-574-3p represents a unique feature of aberrant expression profile of women with a prior exposure to GDM. Screening of particular microRNAs may stratify a high-risk group of mothers with a history of GDM who might benefit from implementation of early primary prevention strategies.

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“…Many of the difficulties are due to biologic restrictions regarding which markers are able to cross the blood–brain barrier as well as the lack of specificity for neurologic disease over nonspecific acute phase responses. Recently, there has been interest in brain‐derived exosomes that cross the blood–brain barrier, resulting in peripheral blood‐based “liquid brain biopsies”3 in contrast with studies that have examined total peripheral exosomes 4, 5, 6. Neural exosome protein cargo‐based diagnostics are promising blood biomarkers of chronic neurologic diseases such as Alzheimer's7, 8, 9, 10, 11, 12 and Parkinson's diseases 13.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, there has been interest in brain-derived exosomes that cross the bloodbrain barrier, resulting in peripheral blood-based "liquid brain biopsies" 3 in contrast with studies that have examined total peripheral exosomes. [4][5][6] Neural exosome protein cargo-based diagnostics are promising blood biomarkers of chronic neurologic diseases such as Alzheimer's [7][8][9][10][11][12] and Parkinson's diseases. 13 However, to our knowledge, there have been no clinical studies in humans to evaluate the potential of brain-derived exosomes isolated from peripheral blood in the diagnosis and characterization of acute brain injury.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Potential of Neural Exosome Cargo as Biomarkers for Acute Brain Injury

Goetzl

Merabova

Darbinian

et al. 2017

Ann Clin Transl Neurol

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ObjectiveNeuronal exosomes purified from peripheral blood samples have been proposed as diagnostic tool in the setting of acute brain injury but never tested clinically. We hypothesized that exosome protein biomarkers would change over time following acute hypoxic brain injury and would predict response to therapy.MethodsSynaptopodin (SYNPO), an actin‐associated protein present in postsynaptic spines, was evaluated as a potential biomarker as well as: synaptophysin, neuron‐specific enolase, and mitochondrial cytochrome c oxidase. A secondary analysis was performed on neonatal samples collected at 8, 10, and 14 h after the initiation of therapeutic‐controlled hypothermia for acute hypoxic–ischemic encephalopathy (n = 14). Neuronal exosomes were purified from serum and protein levels were quantified using standard ELISA methods. The primary study outcomes were length of stay (LOS), discharge on seizure medication (DCMED), and composite neuroimaging score (NIS).ResultsThe slope of change in neuronal exosome SYNPO between 8 and 14 h appeared to be the most promising biomarker for all three clinical study outcomes. SYNPO was highly correlated with LOS (−0.91, P < 0.001). SYNPO increased in 6/8 without DCMED and was worse or neutral in 5/5 with DCMED (P = 0.02). All four neonates with an abnormal NIS had neutral or decreasing SYNPO (P = 0.055). Other candidate biomarkers were not associated with outcomes.InterpretationThis report provides the first clinical evidence that neural exosomes turn over rapidly enough in the peripheral circulation to be used as a “troponin‐like” test following acute brain injury. Optimal sampling and biomarkers likely vary with type of brain injury.

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Circulating MicroRNAs as Novel Biomarkers of Stenosis Progression in Asymptomatic Carotid Stenosis

Cited by 80 publications

References 32 publications

Extracellular microRNA 130b‐3p inhibits eCIRP‐induced inflammation

Extracellular microRNA 130b‐3p inhibits eCIRP‐induced inflammation

Diabetes Mellitus and Cardiovascular Risk Assessment in Mothers with a History of Gestational Diabetes Mellitus Based on Postpartal Expression Profile of MicroRNAs Associated with Diabetes Mellitus and Cardiovascular and Cerebrovascular Diseases

Diagnostic Potential of Neural Exosome Cargo as Biomarkers for Acute Brain Injury

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