Abstract
Lipoprotein(a) [Lp(a)] is an inherited and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. Use of stable isotope tracers and compartmental modelling has provided deeper understanding of the physiology and pathophysiology of Lp(a) metabolism in humans, and the mode of action of lipid-regulating agents. Kinetic data have demonstrated that newly synthesized Lp(a)-apolipoprotein (apo) B-100 and Lp(a)-apo(a) are secreted as a holoparticle, with tightly coupled apo(a) and apoB-100 residence times in the circulation. In subjects with normal or high Lp(a) concentrations, the plasma Lp(a) concentration is predominantly determined by the rate of production of Lp(a) particles, irrespective of apo(a) isoform size and background therapy with statins. Lp(a) particle catabolism may only play a modest role in determining Lp(a) concentration in subjects with normal Lp(a) concentration or larger apo(a) isoform size. Kinetic studies also show that niacin and cholesteryl ester transfer protein inhibitors lower plasma Lp(a) concentration by increasing the clearance or catabolism of apo(a), whereas apoB antisense oligonucleotides lower plasma Lp(a) concentration by decreasing hepatic production. Proprotein convertase subtilisin kexin type 9 inhibitors can lower plasma Lp(a) concentration by a dual mode of action involving both increased clearance and decreased production of apo(a), depending on background Lp(a) concentration and/or statin use. Further studies of RNA therapeutics targeted at apo(a), angiopoietin-like 3 and apoC-III on the metabolism of Lp(a) and other lipoproteins will further our understanding of these therapies in decreasing the development of ASCVD.KeywordsApolipoprotein(a)Atherosclerotic cardiovascular diseaseFractional catabolic rateLipoprotein(a)Production rateProprotein convertase subtilisin kexin type 9Stable isotopeStatins
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
