Recent dynamic studies of the metabolism of atherogenic lipoproteins: elucidating the mode of action of new therapies

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: LDL, triglyceride-rich lipoprotein (TRL) and lipoprotein(a) [Lp(a)] particles are the key atherogenic lipoproteins. Deranged metabolism of these lipoproteins accounts for a spectrum of clinically important dyslipidemias, such as FH, elevated Lp(a) and diabetic dyslipidemia. We review the findings from recent dynamic and tracer studies that have contributed to expanding knowledge in this field. RECENT FINDINGS: Deficiency in LDL receptor activity does not only impair the catabolism of LDL-apoB-100 in FH, but also induces hepatic overproduction and decreases catabolism of TRLs. Patients with elevated Lp(a) are characterized by increased hepatic secretion of Lp(a) particles. Elevation of TRLs in diabetes is partly mediated by increased production of apoB-48 and apoC-III, and impaired clearance of apoB-48 in the postprandial state. Tracer kinetic studies show that proprotein convertase subtilisin/kexin type 9 mAbs alone or in combination with statin can increase the catabolism and decrease production of LDL and Lp(a) particles. By contrast, angiopoietin-like protein 3 inhibitors (e.g. evinacumab) reduce VLDL production and increase LDL clearance in FH. Glucagon-like peptide-1 receptor agonists can improve diabetic dyslipidemia by increasing the catabolism of apoB-48 and decreasing the production of apoB-48 and apoC-III. SUMMARY: Dynamic studies of the metabolism of atherogenic lipoproteins provide new insight into the nature of dyslipidemias and point to how new therapies with complementary modes of action may have maximal clinical impact.

Original languageEnglish
Pages (from-to)378-385
Number of pages8
JournalCurrent Opinion in Lipidology
Volume32
Issue number6
DOIs
Publication statusPublished - 1 Dec 2021

Fingerprint

Dive into the research topics of 'Recent dynamic studies of the metabolism of atherogenic lipoproteins: elucidating the mode of action of new therapies'. Together they form a unique fingerprint.

Cite this