Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Mar:69:101685.
doi: 10.1016/j.molmet.2023.101685. Epub 2023 Feb 4.

VLDL receptor gene therapy for reducing atherogenic lipoproteins

Ronald M Krauss  1 , Jonathan T Lu  2 , Joseph J Higgins  2 , Cathryn M Clary  2 , Ray Tabibiazar  2
Affiliations
Review

VLDL receptor gene therapy for reducing atherogenic lipoproteins

Ronald M Krauss et al. Mol Metab. 2023 Mar.

Abstract

Over the past 40 years, there has been considerable research into the management and treatment of atherogenic lipid disorders. Although the majority of treatments and management strategies for cardiovascular disease (CVD) center around targeting low-density lipoprotein cholesterol (LDL-C), there is mounting evidence for the residual CVD risk attributed to high triglyceride (TG) and lipoprotein(a) (Lp(a)) levels despite the presence of lowered LDL-C levels. Among the biological mechanisms for clearing TG-rich lipoproteins, the VLDL receptor (VLDLR) plays a key role in the trafficking and metabolism of lipoprotein particles in multiple tissues, but it is not ordinarily expressed in the liver. Since VLDLR is capable of binding and internalizing apoE-containing TG-rich lipoproteins as well as Lp(a), hepatic VLDLR expression has the potential for promoting clearance of these atherogenic particles from the circulation and managing the residual CVD risk not addressed by current lipid lowering therapies. This review provides an overview of VLDLR function and the potential for developing a genetic medicine based on liver-targeted VLDLR gene expression.

Keywords: Gene therapy; Lipid disorders; Triglycerides; VLDL; VLDL receptor; lipoprotein(a).

PubMed Disclaimer

Figures

Figure 1
Figure 1
Role of hepatic VLDL receptor expression in the clearance of atherogenic particles. Overview of the pathways by which hepatic VLDL receptor expression may increase plasma clearance of atherogenic VLDL remnant and Lp(a) particles. The VLDL receptor can promote hepatic uptake of VLDL remnants via binding to apoE, and this shunt pathway can limit further remnant processing, resulting in reduced LDL production. Lp(a) has also been shown to be a ligand for the VLDL receptor, and thus hepatic VLDL receptor expression would be expected to increase plasma clearance and reduce concentrations of Lp(a) particles. VLDL: very low-density lipoprotein. LDL: low-density lipoprotein. Lp(a): lipoprotein a. apoC: apolipoprotein C. apoB-100: apolipoprotein B-100. apoE: apolipoprotein E.
See this image and copyright information in PMC

References

    1. Tóth P.P., Potter D., Ming E.E. Prevalence of lipid abnormalities in the United States: the National Health and Nutrition examination survey 2003-2006. Journal of Clinical Lipidology. 2012;6:325–330. - PubMed
    1. Soppert J., Lehrke M., Marx N., Jankowski J., Noels H. Lipoproteins and lipids in cardiovascular disease: from mechanistic insights to therapeutic targeting. Adv Drug Deliv Rev. 2020;159:4–33. - PubMed
    1. Pedersen S.B., Langsted A., Nordestgaard B.G. Nonfasting mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis. JAMA Intern Med. 2016;176:1834–1842. - PubMed
    1. Michos E.D., McEvoy J.W., Blumenthal R.S. Lipid management for the prevention of atherosclerotic cardiovascular disease. N Engl J Med. 2019;381:1557–1567. - PubMed
    1. Silverman M.G., Ference B.A., Im K., Wiviott S.D., Giugliano R.P., Grundy S.M., et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. J Am Med Assoc. 2016;316:1289–1297. - PubMed

Publication types