Key result
PCSK9 inhibitors reduce LDL-C levels and likely improve cardiovascular outcomes in dyslipidemia.
Answers are grounded in this paper and cite their sources.
Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted zymogen expressed primarily in the liver. PCSK9 circulates in plasma, binds to cell surface low-density lipoprotein (LDL) receptors, is internalized, and then targets the receptors to lysosomal degradation. Studies of naturally occurring PCSK9 gene variants that caused extreme plasma LDL cholesterol (LDL-C) deviations and altered atherosclerosis risk unleashed a torrent of biological and pharmacological research. Rapid progress in understanding the physiological regulation of PCSK9 was soon translated into commercially available biological inhibitors of PCSK9 that reduced LDL-C levels and likely also cardiovascular outcomes. Here we review the swift evolution of PCSK9 from novel gene to drug target, to animal and human testing, and finally to outcome trials and clinical applications. In addition, we explore how the genetics-guided path to PCSK9 inhibitor development exemplifies a new paradigm in pharmacology. Finally, we consider some potential challenges as PCSK9 inhibition becomes established in the clinic.
No takes yet. Share an insight, caveat, or question.
Burke et al. (2016) conducted a review in Dyslipidemia and atherosclerosis. PCSK9 inhibitors was evaluated on LDL-C levels and cardiovascular outcomes. PCSK9 biological inhibitors reduce plasma LDL-C levels and likely improve cardiovascular outcomes in dyslipidemia (narrative review; no quantitative trial data reported in abstract).
Synapse has enriched 10 related papers. Consider them for comparative context: