Abstract Number: PB0439
Meeting: ISTH 2020 Congress
Theme: Diagnostics and OMICs » Biomarkers of Thrombosis and Hemostasis
Background: Cardiovascular disease (CVD) is a major cause of mortality among people with type 2 diabetes (T2DM).
Aims: We performed gene expression profiling (GEP) from T2DM patients plasma that had developed a major cardiac events during 6 years follow up, compared to patients that had not. Prognostic ability was assesed of selected circulating miRNAs to predict CV complication.
Methods: Six patients per group were randomly selected, from 304 T2DM patients from AVOCADO study. RNA extraction: mirVANA PARIS Kit, quality of RNA check: fluorometric assay. GEP analysis: Clariom D pico chips, Affymetrix. PCR validation in 238 patients, Taqman universal. MiRNA related to platelet function/antiplatelet treatment were chosen among those with the most relevant modulation between the groups.
Results: Profiling results showed a significant modulation involved in: i) EIF2 ii) EIF4 and iii) mTOR signaling in the development of cardiovascular complications. In fact, a highly significant differential expression was found both at unpaired and paired analysis after matching samples for sex, age and cardiovascular risk profile. MiR-223, miR-126, Let-7e, miR-16, and miR-125a-3p were measured in 283 patients (47 patients with primary end point). We found that miR-126 (p< 0.000), Let-7e (p< 0.000), miR-16 (p=0.003), and miR-125a-3p (p=0.001) were able to predict future occurrence of the primary endpoint. MiR-16 and miR-125a-3p showed week positive correlation with hsCRP levels
(r = 0.190, p =0.005 and r=0.166, p=0.013, respectively). Besides, miR-223 were positively correlated with HbA1c
(r = 0.147, p =0.027).
Conclusions: Our results demonstrate a strong association between dysfunction of key canonical pathways, such as EIF2, EIF4 and mTOR signaling pathway and the risk of major cardiovascular complications in T2DM patients. Additionally, miR-126, Let-7e, miR-16, and miR-125a-3p might be useful for the clinical risk assessment during the follow up in high risk patients with chronic inflammatory conditions, such as diabetes, reflecting the residual risk to guide their clinical management. Supported by Polish Science Center “Preludium” 2017/25/N/NZ5/00545
[Heatmap, Microarray results from the Affymetrix GeneChip miRNA 4.0 Array]
[Comparison of miRNA levels based on primary end points. miR-126 (p<0.000), Let-7e (p<0.000), miR-16 (p=0.003), and miR-125a-3p (p=0.001).]
To cite this abstract in AMA style:
Eyileten C, Pordzik J, Soplinska A, Jarosz-Popek J, Czajka P, Wicik Z, Wolska M, Liu W-, De Rosa S, Mirowska-Guzel D, Postula M. Canonical Signaling Pathways Dysfunctions in the Development of Major Cardiovascular Complications, Circulating Micrornas as Novel Biomarkers and their Link to Inflammation in Diabetic Patients [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/canonical-signaling-pathways-dysfunctions-in-the-development-of-major-cardiovascular-complications-circulating-micrornas-as-novel-biomarkers-and-their-link-to-inflammation-in-diabetic-patients/. Accessed September 21, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/canonical-signaling-pathways-dysfunctions-in-the-development-of-major-cardiovascular-complications-circulating-micrornas-as-novel-biomarkers-and-their-link-to-inflammation-in-diabetic-patients/