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
. 2021 Apr 29;23(6):29.
doi: 10.1007/s11883-021-00928-1.

Reverse Cholesterol Transport Dysfunction Is a Feature of Familial Hypercholesterolemia

Joan Carles Escolà-Gil  1   2   3 , Noemí Rotllan  4   5 , Josep Julve  4   5   6 , Francisco Blanco-Vaca  5   6   7
Affiliations
Review

Reverse Cholesterol Transport Dysfunction Is a Feature of Familial Hypercholesterolemia

Joan Carles Escolà-Gil et al. Curr Atheroscler Rep. .

Abstract

Purpose of review: We seek to establish whether high-density lipoprotein HDL metabolism and reverse cholesterol transport (RCT) impairment is an intrinsic feature of familial hypercholesterolemia (FH).

Recent findings: RCT from macrophages (m-RCT), a vascular cell type of major influence on atherosclerosis, is impaired in FH due to defective low-density lipoprotein receptor (LDLR) function via both the HDL- and LDL-mediated pathways. Potential mechanisms include impaired HDL metabolism, which is linked to increased LDL levels, as well as the increased transport of cellular unesterified cholesterol to LDL, which presents a defective catabolism. RCT dysfunction is consistently associated with mutation-positive FH linked to decreased HDL levels as well as impaired HDL remodeling and LDLR function. It remains to be explored whether these alterations are also present in less well-characterized forms of FH, such as cases with no identified mutations, and whether they are fully corrected by current standard treatments.

Keywords: Autosomal dominant hypercholesterolemia; HDL; LDL receptor; Macrophage.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
    1. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478–3490a. - PubMed - PMC
    1. Talmud PJ, Shah S, Whittall R, Futema M, Howard P, Cooper JA, et al. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study. Lancet. 2013;381(9874):1293–301. - PubMed
    1. Martin-Campos JM, Ruiz-Nogales S, Ibarretxe D, et al. Polygenic markers in patients diagnosed of autosomal dominant hypercholesterolemia in catalonia: distribution of weighted LDL-c-raising SNP scores and refinement of variant selection. Biomedicines. 2020;8(9):353. In line with previous findings of different groups, the increased LDL genetic score based on selected SNPs in mutation-negative FH patients suggest the existence of polygenic forms of the disease.
    1. Kontush A. HDL and reverse remnant-cholesterol transport (RRT): Relevance to cardiovascular disease. Trends Mol Med. 2020;26(12):1086–100. This review proposes a potential novel pathway that explains the U-shaped relationship between plasma HDL-C levels and cardiovascular disease via the impairment of the transfer of unesterified cholesterol from triglyceride-rich lipoproteins to HDL. - PubMed
    1. Rosales C, Gillard BK, Xu B, Gotto AM Jr, Pownall HJ. Revisiting reverse cholesterol transport in the context of high-density lipoprotein free cholesterol bioavailability. Methodist Debakey Cardiovasc J. 2019;15(1):47–54. This review hypothesizes that an increased bioavailability of unesterified cholesterol in dysfunctional HDL would promote the excess transfer of this molecule to cells, thus constituting a potential proatherogenic mechanism. - PubMed - PMC

Publication types

LinkOut - more resources