Reverse Cholesterol Transport Dysfunction Is a Feature of Familial Hypercholesterolemia

Author:

Escolà-Gil Joan CarlesORCID,Rotllan NoemíORCID,Julve JosepORCID,Blanco-Vaca FranciscoORCID

Funder

Instituto de Salud Carlos III

Fundació la Marató de TV3

Ministerio de Ciencia, Innovación y Universidades

Publisher

Springer Science and Business Media LLC

Subject

Cardiology and Cardiovascular Medicine

Reference61 articles.

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.

2. 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.

3. 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.

4. 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.

5. 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.

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