The Role of miR-342 in Vascular Health. Study in Subclinical Cardiovascular Disease in Mononuclear Cells, Plasma, Inflammatory Cytokines and PANX2 (original) (raw)
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Clinical laboratory, 2018
Atherosclerosis is a progressive inflammatory disease and is the main underlying mechanism of coronary artery disease (CAD). Immune system cells and cytokines play pivotal roles in the development of atherosclerosis. Several studies have shown the role of microRNA in the inflammatory processes of atherosclerosis, and miR-342-5p has been shown to be involved in macrophage activation during atherosclerosis and cytokine secretion. But until now, there has been no data regarding the association of miR-342-5p with CAD and inflammatory cytokines. This case control study was conducted on 82 CAD patients and 80 controls. Peripheral blood mononuclear cell (PBMC) miR-342-5p expression and gene expression of IL-6 and TNF-α were evaluated using real timePCR. Also, the serum levels of IL-6 and TNF-α were measured using ELISA kits. The results demonstrated a higher expression of miR-342-5p in CAD patients compared to controls (p < 0.001). Moreover, logistic regression revealed an increased ris...
Stem Cell Research & Therapy
Background In spite of clinical progress, cardiovascular disease (CVD) remains the predominant cause of mortality worldwide. Overexpression studies in animals have proven miR-424-5p to have anti-angiogenic properties. As type 1 diabetes mellitus (T1DM) without CVD displays endothelial dysfunction and reduced circulating endothelial progenitor cells (cEPCs), it offers a model of subclinical CVD. Therefore, we explored miR-424-5p, cytokines and vascular health in T1DM. Methods Twenty-nine well-controlled T1DM patients with no CVD and 20-matched controls were studied. Cytokines IL8, TNF-α, IL7, VEGF-C, cEPCs/CD45dimCD34+CD133+ cells and ex-vivo proangiogenic cells (PACs)/fibronectin adhesion assay (FAA) were measured. MiR-424-5p in plasma and peripheral blood mononuclear cells (PBMC) along with mRNAs in PBMC was evaluated. Results We found an elevation of IL7 (p = 0.008), IL8 (p = 0.003), TNF-α (p = 0.041), VEGF-C (p = 0.013), upregulation of mRNA CXCR1 (p = 0.009), CXCR2 (p
2021
Background: Coronary artery disease (CAD) is considered to be one of the most pivotal causes of death in the world. Over the past two decades, significant changes occurred in diagnosis, prognosis, and treatment of CAD, which has helped reduce mortality rates. miRNAs are a class of more than 5000 non-encoding RNA molecules (21 to 25 nucleotides across the length) that regulate the complex biological processes. Today, miRNAs are used to study cardiovascular diseases. In the present study, the expression of miR-146a،miR-27a ،miR-149 and miR-34a in plasma suffering from CAD and control group were investigated. Methods and Results: The present research was performed on 30 men with coronary artery stenosis (CAD) and 30 healthy men as controls. The expression levels of miR-146a, miR-27a, miR-149 and miR-34a in the plasma of patients with CAD and control group were measured using real-time PCR. Also, the correlation between the expression of circulating miRNAs levels and biochemical LDL-C, ...
The Impact of MiR-33a-5p Inhibition in Pro-Inflammatory Endothelial Cells
Diseases
Evidence suggests cholesterol accumulation in pro-inflammatory endothelial cells (EC) contributes to triggering atherogenesis and driving atherosclerosis progression. Therefore, inhibiting miR-33a-5p within inflamed endothelium may prevent and treat atherosclerosis by enhancing apoAI-mediated cholesterol efflux by upregulating ABCA1. However, it is not entirely elucidated whether inhibition of miR-33a-5p in pro-inflammatory EC is capable of increasing ABCA1-dependent cholesterol efflux. In our study, we initially transfected LPS-challenged, immortalized mouse aortic EC (iMAEC) with either pAntimiR33a5p plasmid DNA or the control plasmid, pScr. We detected significant increases in both ABCA1 protein expression and apoAI-mediated cholesterol efflux in iMAEC transfected with pAntimiR33a5p when compared to iMAEC transfected with pScr. We subsequently used polymersomes targeting inflamed endothelium to deliver either pAntimiR33a5p or pScr to cultured iMAEC and showed that the polymersome...
Decreased Serum Level of miR-146a as Sign of Chronic Inflammation in Type 2 Diabetic Patients
PLoS ONE, 2014
Background: There is increasing evidence that chronic inflammation is an important determinant in insulin resistance and in the pathogenesis of type 2 diabetes (T2D). MicroRNAs constitute a newly discovered system of cell regulation and in particular two microRNAs (miR-146a and miR-155) have been described as regulators and biomarkers of inflammation. Aim: To determine a putative association between the levels of miR-146a and miR-155 in serum of T2D patients, clinical parameters and serological indicators of inflammation. Methods: We performed quantitative Real Time PCR (qPCR) of microRNAs from serum (56 Ecuadorian T2D ambulatory patients and 40 non-diabetic controls). In addition, we evaluated T2D-related serum cytokines.chemokines and growth factors using a commercially available multi-analyte cytometric bead array system. We correlated outcomes to clinical parameters, including BMI, HbA1c and lipid state. Results: The Ecuadorian non-diabetic controls appeared as overweight (BMI.25: patients 85%, controls 82.5%) and as dyslipidemic (hypercholesterolemia: patients 60.7%, controls 67.5%) as the patients.
MicroRNA-34a: a new player in arterial inflammaging
Rna Disease, 2015
Arterial inflammaging highly contributes to cardiovascular morbidity and mortality. As vascular cells age they become senescent and sustain a chronic low grade sterile inflammation by acquiring a senescence-associated secretory phenotype (SASP). The molecular mechanisms leading to the phenotypic changes affecting endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are also relevant for the pathogenesis of vascular diseases, such as atherosclerosis and hypertension. Therefore, unravelling the etiology of vascular inflammaging becomes of crucial importance. MicroRNAs (miRNAs) are small non-coding negative post-transcriptional regulator that are emerging as promising drug targets. MicroRNA-34a (miR-34a) had been implicated in tissues aging and endothelial and endothelial progenitor cells senescence. Our recent work showed that this miRNA is upregulated in aged mouse aortas as well as in senescent VSMCs. Conversely, its target SIRT1 is downregulated in the same specimens. We also found that miR-34a can inhibit VSMCs proliferation and induce VSMCs senescence, the latter by the direct regulation of SIRT1. Notably, for the first time, we demonstrated that miR-34a is also able to modulate the SASP by inducing the transcriptional expression of a subset of pro-inflammatory factors in a SIRT1-independent manner. These data support a model in which the age-dependent upregulation of miR-34a, by affecting senescence and inflammation of vascular cells, could play a causal role to arterial dysfunctions. Hence, further studies are necessary to unravel miR-34a-dependent mechanisms leading to arterial inflammaging in order to develop an effective strategy for age-related cardiovascular complications.
Medicina, 2021
Background and Objectives: Tumor necrosis factor alpha (TNF-α) is proatherogenic and associated with the risk of acute ischemic events, although the mechanisms that regulate TNF-α expression in stable coronary artery disease (SCAD) are not fully understood. We investigated whether metabolic, inflammatory, and epigenetic (microRNA (miRNA)) markers are associated with TNF-α expression in SCAD. Materials and Methods: Patients with SCAD were prospectively recruited and their metabolic and inflammatory profiles were assessed. TNF-α levels were assessed using an enzyme-linked immunosorbent assay. The relative expression of six circulating miRNAs associated with the regulation of inflammation and/or atherosclerosis was determined. Results: Of the 24 included patients with the mean age of 65 (9) years, 88% were male, and 54% were diabetic. The TNF-α levels were (median (interquartile range)) 1.0 (0.7–1.1) pg/mL. The percentage of glycosylated hemoglobin (r = 0.418, p = 0.042), serum triglyc...
Oncotarget, 2015
Innovative biomarkers are required to manage type 2 diabetic patients (T2DM). We focused our study on miR-126-3p and miR-21-5p levels, as biomarkers of endothelial function and inflammation. MiRNAs levels were measured in plasma from 107 healthy subjects (CTR) and 193 diabetic patients (T2DM), 76 without (T2DM NC) and 117 with (T2DM C) complications.When diabetic complication were analysed as a whole, miR-126-3p and miR-21-5p levels declined significantly from CTR to T2DM NC and T2DM C patients. When miRNAs levels were related to specific complications, significantly higher miR-21-5p levels (0.46 ± 0.44 vs. 0.26±0.33, p < 0.001) and significant lower miR-126-3p levels (0.21±0.21 vs. 0.28±0.22, p = 0.032) were found in T2DM with previous major cardiovascular events (MACE) vs. all the others T2DM patients.To confirm these results we focused on circulating angiogenic cells (CACs) from a subgroup of 10 CTR, 15 T2DM NC and 15 T2DM patients with MACE. CACs from T2DM patients expressed ...