Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Columbia University Irving Medical Center, College of Physicians and Surgeons, Department of Medicine, Division of Preventive Medicine and Nutrition, New York, NY, USA.
Atherosclerosis. 2024 Apr;391:117474. doi: 10.1016/j.atherosclerosis.2024.117474. Epub 2024 Feb 13.
High plasma lipoprotein (a) [Lp(a)] levels are associated with increased atherosclerotic cardiovascular disease (ASCVD), in part attributed to elevated inflammation. High plasma Lp(a) levels inversely correlate with apolipoprotein (a) [(APO(a)] isoform size. APO(a) isoform size is negatively associated with APO(a) production rate (PR) and positively associated with APO(a) fractional catabolic rate (FCR). We asked whether APO(a) PR and FCR (kinetics) are associated with plasma levels of interleukin (IL)-6 and IL-18, pro-inflammatory interleukins that promote ASCVD.
We used samples from existing data of APO(a) kinetic studies from an ethnically diverse cohort (n = 25: 10 Black, 9 Hispanic, and 6 White subjects) and assessed IL-6 and IL-18 plasma levels. We performed multivariate linear regression analyses to examine the relationships between predictors APO(a) PR or APO(a) FCR, and outcome variables IL-6 or IL-18. In these analyses, we adjusted for parameters known to affect Lp(a) levels and APO(a) PR and FCR, including race/ethnicity and APO(a) isoform size.
APO(a) PR and FCR were positively associated with plasma IL-6, independent of isoform size, and dependent on race/ethnicity. APO(a) PR was positively associated with plasma IL-18, independent of isoform size and race/ethnicity. APO(a) FCR was not associated with plasma IL-18.
Our studies demonstrate a relationship between APO(a) PR and FCR and plasma IL-6 or IL-18, interleukins that promote ASCVD. These studies provide new insights into Lp(a) pro-inflammatory properties and are especially relevant in view of therapies targeting APO(a) to decrease cardiovascular risk.
高血浆脂蛋白（a）[Lp(a)]水平与动脉粥样硬化性心血管疾病（ASCVD）的风险增加相关，部分原因是炎症水平升高。高血浆 Lp(a)水平与载脂蛋白（a）[APO(a)]的异构体大小呈负相关。APO(a)异构体大小与 APO(a)产生率（PR）呈负相关，与 APO(a)的分代谢率（FCR）呈正相关。我们想知道 APO(a)PR 和 FCR（动力学）是否与白细胞介素（IL）-6 和 IL-18 的血浆水平相关，这些促 ASCVD 的促炎细胞因子。
我们使用了来自种族多样化队列的现有 APO(a)动力学研究样本（n=25：10 名黑人、9 名西班牙裔和 6 名白人），并评估了 IL-6 和 IL-18 的血浆水平。我们进行了多元线性回归分析，以检查预测变量 APO(a)PR 或 APO(a)FCR 与结果变量 IL-6 或 IL-18 之间的关系。在这些分析中，我们调整了已知影响 Lp(a)水平和 APO(a)PR 和 FCR 的参数，包括种族/民族和 APO(a)异构体大小。
APO(a)PR 和 FCR 与血浆 IL-6 呈正相关，与异构体大小无关，但与种族/民族有关。APO(a)PR 与血浆 IL-18 呈正相关，与异构体大小和种族/民族无关。APO(a)FCR 与血浆 IL-18 无关。
我们的研究表明，APO(a)PR 和 FCR 与促 ASCVD 的血浆 IL-6 或 IL-18 之间存在关联。这些研究为 Lp(a)促炎特性提供了新的见解，特别是在针对 APO(a)以降低心血管风险的治疗方面。
