Intercellular miRNA Traffic

Ramanujam, Deepak; Engelhardt, Stefan

doi:10.1161/circresaha.115.306519

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…This result reflects the complex time- and cell type-specificity of miRNA regulation. miR-143-3p is involved in the regulation of the phenotype and function of EC and VSMCs [71, 72], an in the initiation of the inflammatory response in the myocardium [73]. The increased expression of has-miR-143-3p in AMI patients is probably a response to the acute event, as observed in ischemic stroke patients, in which its levels decreased after the acute phase [74].…”

Section: Discussionmentioning

confidence: 99%

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Role of miRNAs induced by oxidized low-density lipoproteins in coronary artery disease: the REGICOR Study

Degano

Subirana

García-Mateo

et al. 2019

Preprint

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Aims: Current risk prediction tools are not accurate enough to identify most individuals at high coronary risk. On the other hand, oxidized low-density lipoproteins (ox-LDLs) and miRNAs are actively involved in atherosclerosis. Our aim was to examine the association of ox-LDL-induced miRNAs with coronary artery disease (CAD), and to assess their predictive capacity of future CAD. Methods and results: Human endothelial and vascular smooth muscle cells were treated with oxidized or native LDLs (nLDL), and their miRNA expression was measured with the miRNA 4.0 array, and analyzed with moderated t-tests. Differently expressed miRNAs and others known to be associated with CAD, were examined in serum samples of 500 acute myocardial infarction (AMI) patients and 500 healthy controls, and baseline serum of 117 incident CAD cases and c 485 randomly-selected cohort participants (case-cohort). Both were developed within the REGICOR AMI Registry and population cohorts from Girona. miRNAs expression in serum was measured with custom OpenArray plates, and analyzed with fold change (age and sex-paired case-control) and survival models (case-cohort). Improvement in discrimination and reclassification by miRNAs was assessed. Twenty-one miRNAs were up- or down-regulated with ox-LDL in cell cultures. One of them, 1 (has-miR-122-5p, fold change=4.85) was upregulated in AMI cases. Of the 28 known CAD-associated miRNAs, 11 were upregulated in AMI cases, and 1 (hsa-miR-143-3p, hazard ratio=0.56 [0.38-0.82]) was associated with CAD incidence and improved reclassification. Conclusion: We identified 2 novel miRNAs associated with ox-LDLs (hsa-miR-193b-5p and hsa-miR-1229-5p), and 1 miRNA that improved reclassification of healthy individuals (hsa-miR-143-3p).

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Section: Discussionmentioning

confidence: 99%

“…In addition, an increase in has-miR-143-3p expression could also stimulate vessel stabilization through the transfer of this miRNA from VSMCs to ECs [76]. On the other hand, miR-143 promotes differentiation and represses proliferation of VSMCs [71], and was downregulated in animal models of atherosclerosis [71], and in CAD patients [77].…”

Section: Discussionmentioning

confidence: 99%

Role of miRNAs induced by oxidized low-density lipoproteins in coronary artery disease: the REGICOR Study

Degano

Subirana

García-Mateo

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…This result reflects the complex time-and cell type-specificity of miRNA regulation. MiR-143-3p is involved in the regulation of the phenotype and function of EC and VSMCs [40,41], and in the initiation of the inflammatory response in the myocardium [42]. The increased expression of hsa-miR-143-3p in AMI patients is probably a response to the acute event [43] and could mediate the initiation of the inflammatory response that is triggered after AMI.…”

Section: Hsa-mir-143-3p Findings and Role In The Vascular Wallmentioning

confidence: 99%

Association of Circulating microRNAs with Coronary Artery Disease and Usefulness for Reclassification of Healthy Individuals: The REGICOR Study

Dégano

Camps

Subirana

et al. 2020

JCM

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Risk prediction tools cannot identify most individuals at high coronary artery disease (CAD) risk. Oxidized low-density lipoproteins (oxLDLs) and microRNAs are actively involved in atherosclerosis. Our aim was to examine the association of CAD and oxLDLs-induced microRNAs, and to assess the microRNAs predictive capacity of future CAD events. Human endothelial and vascular smooth muscle cells were treated with oxidized/native low-density lipoproteins, and microRNA expression was analyzed. Differentially expressed and CAD-related miRNAs were examined in serum samples from (1) a case-control study with 476 myocardial infarction (MI) patients and 487 controls, and (2) a case-cohort study with 105 incident CAD cases and 455 randomly-selected cohort participants. MicroRNA expression was analyzed with custom OpenArray plates, log rank tests and Cox regression models. Twenty-one microRNAs, two previously undescribed (hsa-miR-193b-5p and hsa-miR-1229-5p), were up- or down-regulated upon cell treatment with oxLDLs. One of the 21, hsa-miR-122-5p, was also upregulated in MI cases (fold change = 4.85). Of the 28 CAD-related microRNAs tested, 11 were upregulated in MI cases-1 previously undescribed (hsa-miR-16-5p)-, and 1/11 was also associated with CAD incidence (adjusted hazard ratio = 0.55 (0.35–0.88)) and improved CAD risk reclassification, hsa-miR-143-3p. We identified 2 novel microRNAs modulated by oxLDLs in endothelial cells, 1 novel microRNA upregulated in AMI cases compared to controls, and one circulating microRNA that improved CAD risk classification.

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“…MiR-143 along with its counterpart, miR-145, which were co-transcribed together, were shown to be highly expressed in vascular smooth muscle cells of various organs and essential for controlling contractile phenotype (97,98). Both miR-143 and miR-145 were demonstrated to promote differentiation and suppress proliferation of vascular smooth muscle cells by regulating serum response factor (SRF) to repress factors that promote proliferative smooth muscle phenotype (99).…”

Section: Chapter 5 Discussion and Conclusionmentioning

confidence: 99%

Serum microRNA profile and serum neuron specific enolase, S-100, and interleukin-6 level as biomarkers for differentiating acute vertigo between cerebellar or brainstem infarction and peripheral vertigo

Kijpaisalratana

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Background and PurposeAcute vertigo is a common presentation of inner ear disease. However, it can also be caused by more serious conditions, especially posterior circulation stroke. Differentiation between these 2 conditions by clinical presentations and imaging studies during acute phase can be challenging. This study aims to evaluate the serum microRNA profile and serum neuron specific enolase (NSE), S-100, and interleukin-6 (IL-6) level as potential biomarkers to differentiate between patients with central vertigo due to cerebellar or brainstem infarction and peripheral vertigo.MethodsIn the discovery phase, miRNA expression profiling was performed by Nanostring nCounter Technology in serum of patients with central vertigo due to cerebellar or brainstem infarction (n=3) and peripheral vertigo (n=3) during acute phase within 72 hours after vertigo onset (day 0) and on day 90. MiRNAs that expressed only in acute phase of patients with stroke were selected as potential candidates. Subsequent validation was performed by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) in the serum of patients with posterior circulation stroke (n=23) and peripheral vertigo (n=35). The serum NSE, S100 and interleukin-6 (IL-6) measurements were performed by electrochemiluminescence immunoassay (ECLIA).ResultsIn the discovery phase, miR-342-3p, miR-376-3p, and miR-433-5p were identified by Nanostring nCounter Technology as potential biomarker candidates. In subsequent validation phase, serum miR-433-5p was the only miRNA expressed at significantly high levels in patients with central vertigo during acute phase (median (IQR) central: 92.13 (49.06-183.2) copies/?L vs. peripheral: 53.45 (35.37-102.3) copies/?L, P=0.0056). Only miR-433-5p had discriminative ability to differentiate between central and peripheral vertigo with area under the receiver operating characteristic curve (AUROC) of 0.71. Using a serum miR-433-5p cut off at level >46 copies/?L, the sensitivity and specificity were 87% and 49% respectively. Both S100 (central: 0.111 (0.049-0.335) ?g/L vs. peripheral: 0.054 (0.039-0.082) ?g/L, P=0.005),� and IL-6 central: 7.42 (4.23-14.47) pg/mL vs. peripheral: 2.44 (0.70-4.68) pg/mL, P< 0.001) had significantly higher level in patients with central vertigo.ConclusionThis is the first study to demonstrate the potential of serum miR-433-5p as a biomarker to differentiate between cerebellar or brainstem infarction and peripheral vertigo among patients with acute vertigo. � � �

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Intercellular miRNA Traffic

Cited by 7 publications

References 22 publications

Role of miRNAs induced by oxidized low-density lipoproteins in coronary artery disease: the REGICOR Study

Role of miRNAs induced by oxidized low-density lipoproteins in coronary artery disease: the REGICOR Study

Association of Circulating microRNAs with Coronary Artery Disease and Usefulness for Reclassification of Healthy Individuals: The REGICOR Study

Serum microRNA profile and serum neuron specific enolase, S-100, and interleukin-6 level as biomarkers for differentiating acute vertigo between cerebellar or brainstem infarction and peripheral vertigo

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