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MICRORNA BIOMARKERS OF EARLY CORONARY ATHEROSCLEROSIS IN BABOONS

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title
MICRORNA BIOMARKERS OF EARLY CORONARY ATHEROSCLEROSIS IN BABOONS
author
Livingston, Christopher Wyatt
abstract
Background: The purpose of this study was to identify a panel of microRNA (miRNA) biomarkers of atherosclerosis in baboons, a well characterized model of human atherosclerosis. Early detection of atherosclerosis may facilitate treatment before symptoms develop.Methods: Baboons were fed a high-calorie high-fat challenge diet for two years, then necropsied, and coronary arteries and blood samples collected. We used small RNA sequencing to identify all circulating miRNAs expressed in blood samples. Coronary artery samples were fixed in formalin, stained with Sudan IV, and photographed. ImageJ was used to evaluate the proportion of surface area covered by atherosclerotic lesions (extent of atherosclerosis) in coronary arteries from 68 animals. Data were reproducible from 36 out of the 68 tissues evaluated. Using data from 23 samples for fatty streaks and 13 samples for fibrous plaques, we used Prism 9 to perform simple linear regression to identify expressed miRNAs that correlated with fatty streak and fibrous plaque lesions. The R package DESeq2 was used to identify expressed miRNAs that correlated with extent of lesions after adjusting for age and sex. Results: We identified the four miR-30c-2-3p, miR-411-3p, miR-210-3p, and miR-548b-5p most predictive (lowest p-value) miRNAs for both fatty streaks and fibrous plaques. Analysis of covariance with age and sex resulted in a different set of four miR-128-3p, miR-454-3p, miR-106a-5p, and miR-125-5p most predictive miRNAs. Conclusions: We identified a potential panel of blood miRNA biomarkers of early coronary atherosclerosis in baboons. This work provides the first step for development of a simple blood drop test for early coronary atherosclerosis. However, there is a need for cautious interpretation of the data due to the small sample size analyzed. Future studies will optimize evaluation of lesions in a larger sample size to increase reproducibility.
subject
atherosclerosis
baboons
biomarkers
HCHFD
miRNA
morphometrics
contributor
Karere, Genesio M (advisor)
Langefeld, Carl D (committee member)
date
2024-05-23T08:36:32Z (accessioned)
2024 (issued)
degree
Biomedical Science – MS (discipline)
embargo
2029-05-18 (terms)
2029-05-18 (liftdate)
identifier
http://hdl.handle.net/10339/109464 (uri)
language
en (iso)
publisher
Wake Forest University
type
Thesis

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