scholarly journals Increased miR-142 Levels in Plasma and Atherosclerotic Plaques from Peripheral Artery Disease Patients with Post-Surgery Cardiovascular Events

2020 ◽  
Vol 21 (24) ◽  
pp. 9600
Author(s):  
Teodora Barbalata ◽  
Oriana E. Moraru ◽  
Camelia S. Stancu ◽  
Yvan Devaux ◽  
Maya Simionescu ◽  
...  

There is an intensive effort to identify biomarkers to predict cardiovascular disease evolution. We aimed to determine the potential of microRNAs to predict the appearance of cardiovascular events (CVEs) in patients with peripheral artery disease (PAD) following femoral artery bypass surgery. Forty-seven PAD patients were enrolled and divided into two groups, without CVEs (n = 35) and with CVEs (n = 12), during 1 year follow-up. Intra-surgery atherosclerotic plaques from femoral arteries were collected and the levels of miR-142, miR-223, miR-155, and miR-92a of the primary transcripts of these microRNAs (pri-miRNAs), and gene expression of Drosha and Dicer were determined. Results showed that, in the plaques, miR-142, miR-223, and miR-155 expression levels were significantly increased in PAD patients with CVEs compared to those without CVEs. Positive correlations between these miRNAs and their pri-miRNAs levels and the Dicer/Drosha expression were observed. In the plasma of PAD patients with CVEs compared to those without CVEs, miR-223 and miR-142 were significantly increased. The multiple linear regression analyses revealed significant associations among several plasma lipids, oxidative and inflammatory parameters, and plasma miRNAs levels. Receiver operator characteristic (ROC) analysis disclosed that plasma miR-142 levels could be an independent predictor for CVEs in PAD patients. Functional bioinformatics analyses supported the role of these miRNAs in the regulation of biological processes associated with atherosclerosis. Taken together, these data suggest that plasma levels of miR-142, miR-223, miR-155, and miR-92a can significantly predict CVEs among PAD patients with good accuracy, and that plasma levels of miR-142 can be an independent biomarker to predict post-surgery CVEs development in PAD patients.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Leiherer ◽  
A Muendlein ◽  
C H Saely ◽  
R Laaksonen ◽  
M Laaperi ◽  
...  

Abstract Background Ceramides are enriched in atherosclerotic plaques, and a set of circulating ceramides including Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), and Cer(d18:1/24:0) has recently emerged as predictors of cardiovascular outcomes in coronary artery disease patients. Purpose The purpose of this study was to investigate their power to predict cardiovascular events in patients with peripheral artery disease (PAD). Methods We measured the serum concentrations of the above mentioned ceramides in a cohort of 380 patients with sonographically proven PAD, of whom 107 had type 2 diabetes (T2DM). Prospectively, we recorded 221 cardiovascular events over a mean follow-up time of 6.3±2.3 years. Results Cardiovascular event risk was higher in T2DM patients than in those who did not have diabetes (69 vs. 52%, p=0.001). The ceramides Cer(18:1/16:0) and Cer(18:1/24:1) and the respective ratios Cer(18:1/16:0) / Cer(18:1/24:0) and Cer(18:1/24:1) / Cer(18:1/24:0) were significant predictors of cardiovascular events both univariately and after multivariate adjustment including the presence of T2DM (figure). Conversely, T2DM predicted cardiovascular events independently from the investigated ceramides (adjusted HR 1.76 [1.31–2.35], p<0.001). Conclusion We conclude that the investigated ceramides and T2DM are mutually independent predictors of cardiovascular events in PAD patients.


2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Kerry S Russell ◽  
Denise Yates ◽  
Andrea Feller ◽  
Tianke Wang ◽  
Ping Chen ◽  
...  

Background: Peripheral artery disease (PAD) affects 8.5 million people in the US. PAD patients are at high risk for cardiovascular events, and their quality of life is often significantly impaired by decreased mobility. Interleukin-1β (IL-1β) may play an important role in this disease by promoting inflammatory responses that drive atherosclerotic plaque progression and impair vascular function. We sought to test whether interruption of IL-1β signaling would improve patient mobility and decrease plaque progression in the lower extremities. Methods: 38 patients (mean age 65; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive Canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. Plaque volume in the superficial femoral artery (SFA) was assessed serially using 3.0T MRI. Mobility was assessed serially using the 6-minute walk test (maximum and pain-free walking distance). Results: Canakinumab was safe and well-tolerated. 12 patients discontinued (8 placebo, 4 Canakinumab). MRI data (from 31 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA at either time point in placebo-treated patients; nor was there a change in plaque volume in the Canakinumab-treated group. There was a serial and significant improvement in placebo-adjusted maximum and pain-free walking distance observed as early as 3 months after treatment with Canakinumab (58-meter improvement over placebo in pain-free distance at 3 months, P=0.01). Two placebo-treated patients required peripheral vascular interventions due to progression of disease; however, no Canakinumab-treated patients required revascularization during the study. Canakinumab decreased markers of systemic inflammation (IL-6 and hsCRP). Conclusions: Treatment with Canakinumab may improve maximum and pain-free walk distance in patients with symptomatic PAD. In conjunction with results soon to be reported for the CANTOS trial of Canakinumab for secondary prevention of cardiovascular events, additional studies may provide support that inhibition of IL-1β signaling can improve symptoms and function in this patient population with high unmet need.


Author(s):  
Connie N. Hess ◽  
Marc P. Bonaca

Patients with peripheral artery disease (PAD) are at heightened risk for ischemic events related to atherothrombosis. Antithrombotic therapies can reduce the risk of atherothrombotic events but increase bleeding. Importantly, there is growing appreciation of the heterogeneity in risk profile and effect of antithrombotic therapies in different populations, including those with PAD. Further, patients with PAD are at risk for not only major adverse cardiovascular events but also major adverse limb events, and the drivers of risk for each are different. Within PAD populations, data from trials may be difficult to interpret due to differences among the studies with regards to patient population, clinical settings, and outcomes examined. The acute setting of peripheral revascularization which involves plaque rupture and endothelial disruption confers very high risk of major adverse limb events early postprocedure. Among patients with chronic PAD for whom the goal of antithrombotic therapy is secondary prevention, concomitant coronary artery disease, particularly with prior myocardial infarction, is associated with greatest risk for major adverse cardiovascular events, while prior peripheral revascularization or amputation is associated with greatest risk for major adverse limb events. Understanding of the potential impact of clinical setting and patient risk profile is important to guide evidence-based decisions regarding antithrombotic therapy in patients with PAD. In this article, we provide a contemporary review of data supporting the use of antithrombotic therapy in PAD, as well as a clinical framework for analysis and translation of these data into practice, highlighting areas in need of further investigation.


Author(s):  
Diana Thomas Manapurathe ◽  
Joseph Vaughan Moxon ◽  
Smriti Murali Krishna ◽  
Sophie Rowbotham ◽  
Frank Quigley ◽  
...  

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