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Published on: October 12, 2017
Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Where Do We Stand?
Georgios Tsioulos1, Dimitris Kounatidis2, Natalia G Vallianou3
1Fourth Department of Internal Medicine, Medical School, University General Hospital Attikon, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Insights
Lipoprotein(a) [Lp(a)] is a genetic risk factor for atherosclerotic cardiovascular disease (ASCVD). Novel therapies targeting Lp(a), including antisense oligonucleotides and small interfering RNAs, show promise for treatment.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Pharmacology
Background:
- Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD).
- Lp(a) levels are primarily genetically determined by the LPA gene, leading to lifelong stability.
- Challenges in standardized Lp(a) measurement and its stable levels contribute to limited therapeutic options.
Purpose of the Study:
- To review current knowledge on Lipoprotein(a) [Lp(a)] structure, metabolism, and factors influencing its levels.
- To discuss the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and thrombosis pathogenesis.
- To analyze emerging therapeutic strategies targeting Lp(a), including novel agents and their potential clinical applications.
Main Methods:
- Literature review synthesizing recent data on Lp(a).
- Analysis of Lp(a) structure, metabolism, and genetic determination.
- Evaluation of laboratory measurement techniques for Lp(a).
- Review of existing and novel therapeutic agents targeting Lp(a).
Main Results:
- Lp(a) is a significant, genetically determined risk factor for ASCVD.
- Novel therapeutic agents, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and muvalaplin, are under development.
- These agents target Lp(a) at various levels, offering potential new treatment avenues.
Conclusions:
- Lipoprotein(a) [Lp(a)] plays a critical role in ASCVD pathogenesis.
- Emerging therapies targeting Lp(a) demonstrate significant potential for managing cardiovascular risk.
- Further research and clinical trials are essential to validate the efficacy and safety of these novel agents.
Abstract:
Lipoprotein(a) [Lp(a)] consists of a low-density lipoprotein-like molecule and an apolipoprotein(a) [apo(a)] particle. Lp(a) has been suggested to be an independent risk factor of atherosclerotic cardiovascular disease (ASCVD). Lp(a) plasma levels are considered to be 70-90% genetically determined through the codominant expression of the LPA gene. Therefore, Lp(a) levels are almost stable during an individual's lifetime. This lifelong stability, together with the difficulties in measuring Lp(a) levels in a standardized manner, may account for the scarcity of available drugs targeting Lp(a). In this review, we synopsize the latest data regarding the structure, metabolism, and factors affecting circulating levels of Lp(a), as well as the laboratory determination measurement of Lp(a), its role in the pathogenesis of ASCVD and thrombosis, and the potential use of various therapeutic agents targeting Lp(a). In particular, we discuss novel agents, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) that are currently being developed and target Lp(a). The promising role of muvalaplin, an oral inhibitor of Lp(a) formation, is then further analyzed.
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