1,720,962 research outputs found
Hypertension is a determinant of ABCA1 expression in atherosclerotic plaques from hypercholesterolemic patients
No full textMicroRNA profiling reveals new potetial modulators of insulin resistance and cardiovascular risk in type 2 diabetes
No full textMicroRNA profiling reveals new potential modulators of insulin-resistance in type 2 Diabetes
No full textBackground: Type 2 Diabetes (T2DM) is a chronic disease characterized by an inadequate beta-cell response to the progressive insulin resistance. The tiny mechanism(s) underlying insulin-resistance and increased atherosclerosis burden in T2DM patients are not fully understood. MicroRNAs (miRNAs) are short (20-22 nucleotides of length), endogenous, non-coding, RNAs representing a new class of regulators of gene expression. Remarkably, they are found in all cell type and their presence is clearly detectable in peripheral blood. Currently miRNAs involvement has been demonstrated in many diseases such as cancer, inflammatory and cardiovascular diseases. However, the role of miRNAs in T2DM in humans is not fully elucidated, thus aim of this study was to investigate the plasma miRNAs profile of diabetic patients.
Materials and Methods: blood samples were collected from 11 diabetic patients and 11 matched control patients. T2DM diagnosis was formulated according currently available American Diabetes Association guidelines. We enrolled only drug-naïve patients before starting specific treatment. Patients with active inflammatory diseases, chronic kidney disease and cancer were excluded. RNA was extracted according with previously validated methods, quantified and pooled and a wide microRNA expression profiling was performed (miRNome). Then, some of the miRNAs that were differently expressed between two groups were validated by RealTime-PCR (RT-PCR). Data analyses were performed with deltadelta Ct method. Finally, bioinformatics was used in order to identify the potential targets of these miRNAs.
Results: microarray analysis showed that 4 miRNAs were upregulated whereas 21 miRNAs were downregulated in diabetic patients. Interestingly, RT-PCR validation confirmed a significant downregulation of let-7a (p=0.023) and let-7f (p=0.049). Moreover, we found a significant upregulation of miR-326 (p=0.006). Furthermore, an interesting trend supporting down-regulation of miR-16, miR-21 and let-7g in diabetic patients was found, despite these values did not reach statistical significance probably due the small study population. In silico analysis confirmed that the predicted targets of these miRNAs are able to modulate genes involved in insulin-sensitivity, including Adiponectin and IGF-1 receptor.
Conclusion: this study demonstrated that diabetes is associated with a modulation of the expression of plasma miRNA that are involved in insulin resistance. If confirmed, these findings will contribute to improve our knowledge on diabetes pathophysiology and lead to the identification of new innovative therapeutic approach
MicroRNA profiling reveals new potential modulators of insulin-resistance and cardiovascular risk in type 2 diabetes
No full textBackground: Type 2 Diabetes (T2DM) is a chronic disease characterized
by an inadequate beta-cell response to the progressive insulin
resistance. The tiny mechanism(s) underlying insulin-resistance and
increased atherosclerosis burden in T2DM patients are not fully
understood. MicroRNAs (miRNAs) are short (20–22 nucleotides of
length), endogenous, non-coding, RNAs representing a new class of
regulators of gene expression. Remarkably, they are found in all cell
type and their presence is clearly detectable in peripheral blood.
Currently miRNAs involvement has been demonstrated in many
diseases such as cancer, inflammatory and cardiovascular diseases.
However, the role of miRNAs in T2DM in humans is not fully elucidated,
thus aim of this study was to investigate the plasma miRNAs
profile of diabetic patients.
Materials and Methods: Blood samples were collected from 11
diabetic patients and 11 matched control patients. T2DM diagnosis
was formulated according currently available American Diabetes
Association guidelines. We enrolled only drug-naı ̈ve patients before
starting specific treatment. Patients with active inflammatory diseases,
chronic kidney disease and cancer were excluded. RNA was extracted
according with previously validated methods, quantified and pooled
and a wide microRNA expression profiling was performed (miRNome).
Then, some of the miRNAs that were differently expressed
between two groups were validated by RealTime-PCR (RT-PCR).
Data analyses were performed with deltadelta Ct method. Finally,
bioinformatics was used in order to identify the potential targets of
these miRNAs.
Results: Microarray analysis showed that 4 miRNAs were upregulated
whereas 21 miRNAs were downregulated in diabetic patients.
Interestingly, RT-PCR validation confirmed a significant downregulation
of let-7a (p = 0.023) and let-7f (p = 0.049). Moreover, we
found a significant upregulation of miR-326 (p = 0.006). Furthermore,
an interesting trend supporting down-regulation of miR-16,
miR-21 and let-7 g in diabetic patients was found, despite these
values did not reach statistical significance probably due the small
study population. In silico analysis of predicted targets confirmed that
these miRNAs may modulate genes greatly involved in insulin-signaling
(including Adiponectin, IGF-1 receptor and others),
endothelial function (including PTEN) and linked to cardiovascular
risk (including VLDL receptor, TGF-beta).
Conclusion: This study demonstrated that diabetes is associated with
a modulation of the expression of plasma miRNA that are involved in
insulin resistance and endothelial function. Further studies on these specific miRNAs’ targets are required to understand the molecular
read-out of this modulation. If confirmed, these findings will contribute
to improve our knowledge on diabetes pathophysiology and
lead to the identification of new innovative therapeutic strategies for
T2DM
Effect of Rosuvastatin on MicroRNAs expression in human atherosclerotic plaques: results from Quasar Study
No full textBackground: Statins are competitive inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase and are a leading therapy for the prevention of ischemic events. Although lowering of plasma low-density lipoproteins (LDL) is the most relevant effect, numerous studies suggest many other pleiotropic effects of statins, which involve improving of endothelial function, enhancing atherosclerotic plaque stability and decreasing oxidative stress and inflammation. MicroRNAs are small non-coding RNAs which act as post-transcriptional gene regulators. Growing evidences support the microRNAs involvement in cardiovascular disease and there are tantalizing hints of the effect of statin on microRNAs. The aim of this study is to investigate whether a short-time treatment with low or high dose of rosuvastatin may affect microRNAs expression in human atherosclerotic plaques.
Material and Methods: In the “QUalitative Analysis of plaque Stability After Rosuvastatin therapy in asymptomatic patients enlisted to undergo carotid endoarterectomy” (QUASAR) 70 patients with severe stenosis of the internal carotid artery were randomized to receive a 12 week low (10 mg/day) or high (40 mg/day) doses of rosuvastatin before the elective endoarterectomy. Total RNA was extracted from plaques using Trizol reagent. Pools creation for MiRNome qPCR analysis was carried out using total RNA extracted from respectively 11 selected plaques of rosuvastatin 10 mg and 40 mg groups and from 11 plaques of naive hypercholesterolemic patients (control group). MiRNome qPCR analysis was performed by using miRCURY LNA Universal RT microRNA PCR system. MicroRNAs validation study was performed on all plaques from the pooled samples by qPCR.
Results: MiRNome qPCR analysis of 742 microRNAs on pooled hypercholesterolemic samples versus respectively pooled rosuvastatin 10mg and rosuvastatin 40mg samples showed several microRNAs dysregulated in rosuvastatin groups versus hypercholesterolemic one. We have paid attention on nine microRNAs on the strength of their predicted target genes involved in atherosclerosis. Real-time PCR validation studies on all plaques from the pooled samples showed that both rosuvastatin doses significantly up-regulated mir-9 (p<0.004), mir-20b (p<0.001), mir-133a/b (p=0.001), mir-144 (p<0.001), mir-301a (p=0.01), and mir-377 (p=0.002), respect to hypercholesterolemic patients. Mir-150 and mir-155 were not found significantly down-regulated in the qPCR validation analysis.
Conclusions: These data showed that short-term rosuvastatin treatment may affect microRNAs expression profile in human atherosclerotic plaques. Further studies on their predicted target gene are required to better understand microRNAs involvement in the beneficial effects observed with statin-based lipid lowering therapies
Plasma exosome microRNA profiling unravels a new potential modulator of adiponectin pathway in diabetes: effect of glycemic control
No full textContext: type 2 diabetes is a chronic disease characterized by inadequate beta-cell response to the progressive insulin resistance. MicroRNAs (miRNAs) are short, endogenous, non-coding, RNAs representing a class of powerful gene expression modulators. Previous population studies observed a modulation of circulating miRNAs in diabetic patients; however, little data are presently available on miRNA modulation in diabetic patients naϊve to pharmacological treatment, as well as the effect of glycemic control on this. Objective: we aimed at studying circulating miRNAs expression in diabetic patients naϊve to treatment, and at investigating the influence on this of glycemic control. Design: case-control study. Participants: eighteen treatment naϊve diabetic patients with poor-metabolic control and 12 control patients. Main outcome measures: wide miRNA expression profiling was performed, and the expression of miRNAs found to be dysregulated was then validated by qRT-PCR. Finally, algorithm-identified putative miRNA targets were evaluated by qRT-PCR and ELISA. Results: in diabetic patients, microarray analysis showed that 4 miRNAs are increased, whereas 21 miRNAs are decreased. qRT-PCR validation confirmed the significant up-regulation of miR-326 (p=0.004) and down-regulation of let-7a (p<0.001) and let-7f (p=0.003). Notably, an inverse negative correlation was found between circulating miR-326 and its putative target adiponectin (Δ=-0.479, p=0.009). After 12-months of anti-diabetic treatment, qRT-PCR data analysis showed that miR-326 levels were unaffected, whereas the levels of let-7a and let-7f were significantly increased. Conclusions: treatment naϊve, poorly controlled diabetic patients show a significant dysregulation of miRNAs involved in regulation of the adiponectin pathway, a phenomenon that may be reversed, at least in part, by improved glycemic control
Overexpression of ABCA1 in human plaques exposed to hypercholesterolemia: the role of microRNA modulation
No full textATP-binding cassette transporter A1 (ABCA1) overexpression in hypercholesterolemic plaques: a potential molecular explanation
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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