FH through the retrospectoscopeAfter 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.
Thematic Review Series: Exosomes and Microvesicles: Lipids as Key Components of their Biogenesis and Functions, Cholesterol and the journey of extracellular vesiclesEukaryotic cells employ distinct means to release specific signals and material. Research within the last decade has identified different types of membrane-enclosed structures collectively called extracellular vesicles (EVs) as one of them. EVs fall into two categories depending on their subcellular origin. Exosomes are generated within the endosomal system and reach the extracellular space upon fusion of multivesicular bodies. Microvesicles or microparticles are generated by shedding of the plasma membrane.
The role of lipoprotein (a) in chronic kidney disease: Thematic Review Series: Lipoprotein (a): Coming of Age at LastLipoprotein (a) [Lp(a)] and its measurement, structure and function, the impact of ethnicity and environmental factors, epidemiological and genetic associations with vascular disease, and new prospects in drug development have been extensively examined throughout this Thematic Review Series on Lp(a). Studies suggest that the kidney has a role in Lp(a) catabolism, and that Lp(a) levels are increased in association with kidney disease only for people with large apo(a) isoforms. By contrast, in those patients with large protein losses, as in the nephrotic syndrome and continuous ambulatory peritoneal dialysis, Lp(a) is increased irrespective of apo(a) isoform size.
Cholesteryl ester transfer protein and its inhibitorsMost of the cholesterol in plasma is in an esterified form that is generated in potentially cardioprotective HDLs. Cholesteryl ester transfer protein (CETP) mediates bidirectional transfers of cholesteryl esters (CEs) and triglycerides (TGs) between plasma lipoproteins. Because CE originates in HDLs and TG enters the plasma as a component of VLDLs, activity of CETP results in a net mass transfer of CE from HDLs to VLDLs and LDLs, and of TG from VLDLs to LDLs and HDLs. As inhibition of CETP activity increases the concentration of HDL-cholesterol and decreases the concentration of VLDL- and LDL-cholesterol, it has the potential to reduce atherosclerotic CVD.
Thematic Review Series: Lipid Transfer Proteins ABCG5 and ABCG8: more than a defense against xenosterolsThe elucidation of the molecular basis of the rare disease, sitosterolemia, has revolutionized our mechanistic understanding of how dietary sterols are excreted and how cholesterol is eliminated from the body. Two proteins, ABCG5 and ABCG8, encoded by the sitosterolemia locus, work as obligate dimers to pump sterols out of hepatocytes and enterocytes. ABCG5/ABCG8 are key in regulating whole-body sterol trafficking, by eliminating sterols via the biliary tree as well as the intestinal tract. Importantly, these transporters keep xenosterols from accumulating in the body.