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FH through the retrospectoscope.
| Content Provider | Europe PMC |
|---|---|
| Author | Thompson, Gilbert R. |
| Copyright Year | 2021 |
| Abstract | After training as a gastroenterologist in the UK, the author became interested in lipidology while he was a research fellow in the USA and switched careers after returning home. Together with Nick Myant, he introduced the use of plasma exchange to treat familial hypercholesterolemia (FH) homozygotes and undertook non-steady state studies of LDL kinetics, which showed that the fractional catabolic rate of LDL remained constant irrespective of pool size. Subsequent steady-state turnover studies showed that FH homozygotes had an almost complete lack of receptor-mediated LDL catabolism, providing in vivo confirmation of the Nobel Prize-winning discovery by Goldstein and Brown that LDL receptor dysfunction was the cause of FH. Further investigation of metabolic defects in FH revealed that a significant proportion of LDL in homozygotes and heterozygotes was produced directly via a VLDL-independent pathway. Management of heterozygous FH has been greatly facilitated by statins and proprotein convertase subtilisin/kexin type 9 inhibitors but remains dependent upon lipoprotein apheresis in homozygotes. In a recent analysis of a large cohort treated with a combination of lipid-lowering measures, survival was markedly enhanced in homozygotes in the lowest quartile of on-treatment serum cholesterol. Emerging therapies could further improve the prognosis of homozygous FH; whereas in heterozygotes, the current need is better detection. |
| Related Links | https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7933488&blobtype=pdf |
| ISSN | 00222275 |
| Journal | Journal of Lipid Research [J Lipid Res] |
| Volume Number | 62 |
| PubMed Central reference number | PMC7933488 |
| PubMed reference number | 32651185 |
| e-ISSN | 15397262 |
| DOI | 10.1194/jlr.tr120001001 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2021-02-06 |
| Access Restriction | Open |
| Rights License | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). © 2021 The Author |
| Subject Keyword | atherosclerosis cardiovascular disease cholesterol hyperlipidemia hypolipidemic drugs proprotein convertase subtilisin/kexin type 9 statins, low density lipoprotein receptor lipoprotein (a) apheresis familial hypercholesterolemia CHD, coronary heart disease FCR, fractional catabolic rate FH, familial hypercholesterolemia Lp(a), lipoprotein (a) PCSK9, proprotein convertase subtilisin/kexin type 9 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Endocrinology |
