Low density lipoprotein and total cholesterol levels predict circulating miR-152 expression in males, but not females, in an elderly cohort — University of Technology
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Low density lipoprotein and total cholesterol levels predict circulating miR-152 expression in males, but not females, in an elderly cohort (14220)

Emma L Beckett 1 2 , Martin Veysey 3 , Konsta Duesing 2 , Zoe Yates 4 , Mark Lucock 1
  1. Applied Science (Human Molecular Nutrition), University of Newcastle, Ourimbah, NSW, Australia
  2. Human Nutrition Flagship, CSIRO, North Ryde, NSW, Australia
  3. Teaching and Research Unit, Central Coast Local Health District, Gosford, NSW, Australia
  4. School of Biomedical Sciences and Pharmacy, University of Newcastle, Central Coast, Ourimbah, NSW, Australia

Background: miR-152 has been suggested as a potential biomarker or a therapeutic target for atherosclerotic plaques1. miR-152 is co-expressed in non-classical monocytes and atherosclerotic plaques, with higher expression in plaques than in healthy arteries2. A small study (n=20) demonstrated higher levels of circulating miR-152 in the blood of those with atherosclerosis, compared to healthy controls1, however this is yet to be confirmed in a larger cohort. High low density lipoprotein (LDL) cholesterol levels are accepted to play a significant role in the development of atherosclerosis3, and as such are a potential precursor to the onset of the disease. Circulating biomolecules offer a promising avenue for biomarker investigation, as they are easily accessible for sampling.

Aims/Hypothesis: We aimed to examine the relationship between expression of miR-152 in the circulation, and LDL and total cholesterol levels.

Methods: Participants were part of a retirement aged cohort (n=200, 114 females, 65-94 years of age, median age 75.5) living on the Central Coast of NSW. The age distribution did not vary between males and females. Blood was collected by a trained nurse, and LDL and total cholesterol levels determined by the Hunter Area Pathology Service. Circulating miRNAs were measured in plasma by qRT-PCR. Standard linear regression was used to assess the relationship between circulating miR-152 and blood LDL and total cholesterol levels. Analysis was stratified by gender and adjusted for age.

Results: In males, both LDL (r2= 0.17, p= 0.005) and total cholesterol (r2= 0.13, p= 0.021) were significant partial predictors of circulating miR-152 levels. Increasing LDL and cholesterol levels were associated with increased expression of miR-152 (β=0.35, p=0.001 and β=0.24, p=0.006, respectively). No significant results were found in the females. Age distribution did not vary significantly between genders, and age adjustment did not significantly influence the outcomes of the analyses.

Discussion/Conclusion: We have demonstrated that LDL and total cholesterol levels are significant partial predictors of circulating miR-152 expression in males. When taken with the existing evidence of increased expression in atherosclerotic plaques this supports the findings that suggest miR-152 is a biomarker or a potential therapeutic target in the development of atherosclerosis. This work lays the foundation for investigating the mechanistic links between miR-152 expression, LDL cholesterol, total cholesterol and atherosclerotic plaques.

  1. Wu Y, Huang A, Li T, et al. MiR-152 reduces human umbilical vein endothelial cell proliferation and migration by targeting ADAM17. FEBS letters 2014; 588: 2063-9.
  2. Bidzhekov K, Gan L, Denecke B, et al. microRNA expression signatures and parallels between monocyte subsets and atherosclerotic plaque in humans. Thrombosis and haemostasis 2012; 107: 619-25.
  3. Badimon L, Vilahur G. LDL-cholesterol versus HDL-cholesterol in the atherosclerotic plaque: inflammatory resolution versus thrombotic chaos. Annals of the New York Academy of Sciences 2012; 1254: 18-32.
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