Internal Medicine Unit, Department of Clinical and Experimental Medicine Lipid Center, University of Messina, 98122 Messina, Italy.
Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy.
Biomolecules. 2022 Apr 9;12(4):562. doi: 10.3390/biom12040562.
Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a key regulator of low-density lipoprotein (LDL) metabolism involved in the degradation of the low-density lipoprotein receptor (LDLR) through complex mechanisms. The PCSK9 plasma levels change according to lipid lowering therapy (LLT). Few data exist regarding the role of PCSK9 in vascular damage. We aimed to evaluate the impact of PCSK9 plasma levels on pulse wave velocity (PWV) and the effect of PCSK9 inhibitors (PCSK9-i) on circulating PCSK9 and PWV in a cohort of heterozygous familial hypercholesterolemia (HeFH) subjects. In a previous step, HeFH patients were enrolled and LLT was prescribed according to guidelines. Biochemical analyses and PWV assessment were performed at baseline (T0), after 6 months of high-efficacy statin plus ezetimibe (T1) and after 6 months of PCSK9-i (T2). The PCSK9 levels were evaluated in 26 selected HeFH subjects at the three time points and 26 healthy subjects served as controls for the reference value for PCSK9 plasma levels. The PWV values decreased at each time point in HeFH subjects after LLT starting (8.61 ± 2.4 m/s, −8.7%; p < 0.001 vs. baseline at T1, and 7.9 ± 2.1 m/s, −9.3%; p < 0.001 vs. both T1 and baseline) and it was correlated to PCSK9 (r = 0.411, p = 0.03). The PCSK9 levels increased on statin/EZE therapy (+42.8% at T1) while it decreased after PCSK9-i was started (−34.4% at T2). We noted a significant relationship between PCSK9 levels and PWV changes at T1 and T2. In conclusion, PCSK9 levels were associated with baseline PWV values in HeFH subjects; moreover, we found that PCSK9 level variations seemed to be correlated with PWV changes on LLT. A longer observation time and wider sample size are needed to assess the potential role of PCSK9 plasma levels on the vascular function and remodelling, and to clarify the effects of PCSK9-i in these pathways.
前蛋白转化酶枯草溶菌素 9（PCSK9）是一种关键的低密度脂蛋白（LDL）代谢调节剂，通过复杂的机制参与低密度脂蛋白受体（LDLR）的降解。PCSK9 的血浆水平会根据降脂治疗（LLT）而变化。关于 PCSK9 在血管损伤中的作用，目前的数据较少。我们旨在评估 PCSK9 血浆水平对脉搏波速度（PWV）的影响，以及 PCSK9 抑制剂（PCSK9-i）对杂合家族性高胆固醇血症（HeFH）患者循环 PCSK9 和 PWV 的影响。在之前的步骤中，我们招募了 HeFH 患者，并根据指南开出了 LLT 处方。在基线（T0）、6 个月高效他汀加依折麦布（T1）和 6 个月 PCSK9-i（T2）后进行生化分析和 PWV 评估。在三个时间点评估了 26 名 HeFH 患者的 PCSK9 水平，并选择了 26 名健康受试者作为 PCSK9 血浆水平参考值的对照。HeFH 患者在 LLT 开始后，每个时间点的 PWV 值都降低（8.61±2.4 m/s，−8.7%；p＜0.001 与 T1 时的基线相比，并且 7.9±2.1 m/s，−9.3%；p＜0.001 与 T1 和基线相比），且与 PCSK9 相关（r=0.411，p=0.03）。在他汀/EZE 治疗时，PCSK9 水平升高（T1 时升高 42.8%），而在开始使用 PCSK9-i 后，PCSK9 水平降低（T2 时降低 34.4%）。我们注意到 T1 和 T2 时 PCSK9 水平与 PWV 变化之间存在显著关系。总之，在 HeFH 患者中，PCSK9 水平与基线 PWV 值相关；此外，我们发现 PCSK9 水平的变化似乎与 LLT 时的 PWV 变化相关。需要更长的观察时间和更大的样本量来评估 PCSK9 血浆水平对血管功能和重塑的潜在作用，并阐明 PCSK9-i 在这些途径中的作用。
