Article Impact Level: HIGH Data Quality: STRONG Summary of European Heart Journal, ehad261. https://doi.org/10.1093/eurheartj/ehad261 Dr. Günther Silbernagel et al.
Points
- Apolipoprotein C-II (ApoC-II) is investigated for its role in activating lipoprotein lipase (LPL) and as a potential target for treating hypertriglyceridemia.
- A large-scale epidemiologic study involving 3141 participants explored the relationship between ApoC-II and cardiovascular risk, considering the presence of ApoC-III, an LPL antagonist.
- The study found an inverse J-shaped trend between ApoC-II quintiles and cardiovascular mortality, with the highest risk in the lowest quintile and the lowest risk in the middle quintile.
- Adjusting for various factors, all quintiles, except the lowest one, were associated with decreased cardiovascular mortality.
- Experimental assays revealed a bell-shaped relationship between exogenous ApoC-II and GPIHBP1-LPL activity, emphasizing the importance of optimal ApoC-II concentrations for maximizing enzymatic activity.
Summary
This research paper explored the role of apolipoprotein C-II (ApoC-II) in activating lipoprotein lipase (LPL) and its potential as a target for treating hypertriglyceridemia. The study also investigated the association between ApoC-II and cardiovascular risk, considering the presence of apolipoprotein C-III (ApoC-III), an LPL antagonist. Additionally, the paper aimed to shed light on the mechanism underlying ApoC-II-mediated LPL activation.
The study involved 3141 Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort participants, with a median follow-up period of 9.9 years. Among the participants, 590 died from cardiovascular diseases. ApoC-II levels were measured, and enzymatic activity assays were conducted to examine the activation of the glycosylphosphatidylinositol high-density lipoprotein binding protein 1 (GPIHBP1)–LPL complex using fluorometric lipase and very low-density lipoprotein (VLDL) substrates. The findings showed that ApoC-II concentrations averaged 4.5 mg/dL. The relationship between ApoC-II quintiles and cardiovascular mortality exhibited an inverse J-shaped trend, with the highest risk in the lowest quintile and the lowest risk in the middle quintile. After adjusting for various factors, including ApoC-III, all quintiles, except the first one, were associated with decreased cardiovascular mortality (P < 0.05).
In the experimental assays, the effect of exogenous ApoC-II on GPIHBP1–LPL activity showed a bell-shaped relationship. When an anti-ApoC-II antibody was used, ApoC-II-containing VLDL substrate-based lipase assays demonstrated almost complete inhibition of GPIHBP1–LPL enzymatic activity. These findings suggest optimal ApoC-II concentrations are required for maximal GPIHBP1–LPL enzymatic activity.
Based on the epidemiologic data, the study concluded that increasing low circulating levels of ApoC-II may reduce cardiovascular risk. The inverse J-shaped relationship between ApoC-II quintiles and cardiovascular mortality supports this conclusion. Additionally, the experimental findings highlight the importance of maintaining optimal ApoC-II concentrations for maximizing GPIHBP1–LPL enzymatic activity. These insights contribute to identifying potential therapeutic targets for managing hypertriglyceridemia and mitigating cardiovascular risk.
Link to the article: https://academic.oup.com/eurheartj/advance-article-abstract/doi/10.1093/eurheartj/ehad261/7156982
References Silbernagel, G., Chen, Y. Q., Rief, M., Kleber, M. E., Hoffmann, M. M., Stojakovic, T., Stang, A., Sarzynski, M. A., Bouchard, C., März, W., Qian, Y.-W., Scharnagl, H., & Konrad, R. J. (2023). Inverse association between apolipoprotein C-II and cardiovascular mortality: Role of lipoprotein lipase activity modulation. European Heart Journal, ehad261. https://doi.org/10.1093/eurheartj/ehad261
