FH through the retrospectoscope
| Autor: | Gilbert R. Thompson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
PLASMA-EXCHANGE apheresis Familial hypercholesterolemia 030204 cardiovascular system & hematology CHD coronary heart disease 0601 Biochemistry and Cell Biology Biochemistry DOUBLE-BLIND chemistry.chemical_compound 0302 clinical medicine Endocrinology Thematic Review Series: The Science of FH cardiovascular disease Hyperlipidemia hypolipidemic drugs Medicine hyperlipidemia statins low density lipoprotein receptor familial hypercholesterolemia biology Lipoprotein(a) OPEN-LABEL 1101 Medical Biochemistry and Metabolomics Kexin TURNOVER lipids (amino acids peptides and proteins) Life Sciences & Biomedicine Lipidology Biochemistry & Molecular Biology medicine.medical_specialty APOLIPOPROTEIN-B LOW-DENSITY-LIPOPROTEIN HEART-DISEASE QD415-436 FH familial hypercholesterolemia Hyperlipoproteinemia Type II 03 medical and health sciences proprotein convertase subtilisin/kexin type 9 Internal medicine HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA Science & Technology FCR fractional catabolic rate business.industry Cholesterol EVOLOCUMAB PCSK9 lipoprotein (a) cholesterol Thematic Review Series Cell Biology EFFICACY medicine.disease Lp(a) lipoprotein (a) 030104 developmental biology chemistry LDL receptor biology.protein atherosclerosis business PCSK9 proprotein convertase subtilisin/kexin type 9 |
| Zdroj: | Journal of Lipid Research, Vol 62, Iss, Pp 100036-(2021) Journal of Lipid Research |
| ISSN: | 0022-2275 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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