Abstract
Cardiovascular disease (CVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is commonly used for CVD risk assessment; however, recent research has shown LDL particle (LDL-P) number to be a more sensitive indicator of CVD risk than both LDL-C and non-high-density lipoprotein cholesterol (HDL-C). Described herein are five single stranded DNA aptamers with dissociation constants in the low picomolar range specific to LDL-P and its subfractions. Furthermore, a set of antisense sequences have been developed and characterized that are capable of binding to the best aptamers and undergoing displacement by LDL-P for use in a simple, affordable diagnostic assay.
Highlights
Cardiovascular disease (CVD) remains the leading cause of death worldwide [1]
The initial goal of this project was to identify aptamers that bind selectively to LDL particles with the secondary goal of selecting aptamers that can discriminate between large and fluffy LDL (LF-LDL) and small and dense LDL (SD-LDL) particles
CVD risk assessment for patients remains suboptimal with the urgent need for simpler, faster and lower-cost methods for advanced lipoprotein testing
Summary
Cardiovascular disease (CVD) remains the leading cause of death worldwide [1]. Currently, a lipid panel test, consisting of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides is the standard screening method for CVD risk with a high LDL-C and a low HDL-C level indicating an increased risk of CVD. A high LDL-P is associated with a higher risk of CVD due to the favorable diffusive and aggregative interaction of the particles with vascular walls For those with this discordance, only LDL-P was associated with incident CVD [3]. Several studies suggest LDL-P and its small and dense particle subfraction are superior biomarkers to LDL-C and non-HDL-C for CVD risk assessment and screening [4, 5]. This discordance between LDL-C and LDL-P frequently goes unnoticed in traditional lipid testing. A sizable portion of the population receive therapies when they may not be needed and could potentially be harmful [6]
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