Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, Ferrara, Italy.
Medical Department, Internal Medicine Unit, Azienda Ospedaliera-Universitaria S. Anna, Ferrara, Italy.
Atherosclerosis. 2019 Jun;285:64-70. doi: 10.1016/j.atherosclerosis.2019.04.218. Epub 2019 Apr 11.
Epidemiological data showing that high-density lipoprotein cholesterol (HDL-C) is inversely associated with cardiovascular disease have led to the idea that cholesterol contained in this lipoprotein may be protective. Against, recent evidence suggests that the athero-protection from HDLs may result from other functions, unrelated to the carried cholesterol. HDL accessory proteins, such as paraoxonase 1 (PON1), have been suggested to endows HDL with antioxidant and anti-inflammatory properties and to contribute to the athero-protective function of the lipoprotein. We aimed to evaluate whether extreme fluctuation in HDL-C levels correlates with PON1 activity.
Levels of PON1-related arylesterase and lactonase were assessed in subjects with primary hyperalphalipoproteinemia (HAL, HDL-C>90th percentile), hypoalphalipoproteinemia (HA, HDL-C<10th percentile) and controls. Cholesterol efflux capacity (CEC) through several pathways and other metabolic parameters and markers of vascular disease were also determined.
Despite the marked change in HDL-C and Apoliprotein A1 (APO A1) (p < 0.001 for all comparisons), arylesterase and lactonase were only slightly increased in HAL compared with HA subjects (p < 0.05), but not vs. controls. This change in PON1 activities was no longer significant after adjustment for either HDL-C or APO A1. Both enzymatic activities were positively associated only with aqueous diffusion CEC (r = 0.318, p < 0.05 and r = 0.355, p < 0.05, respectively) and negatively with the presence of plaques (p < 0.05).
We showed that extreme high/low HDL-C levels are not associated with equal increase/decrease in PON1 activities. This enzyme appears to contribute to the HDL role in reverse cholesterol transport and anti-atherosclerosis processes. Further investigation is required to corroborate our findings.
流行病学数据表明，高密度脂蛋白胆固醇（HDL-C）与心血管疾病呈负相关，这导致人们认为这种脂蛋白中的胆固醇可能具有保护作用。然而，最近的证据表明，HDL 的抗动脉粥样硬化作用可能来自于与携带胆固醇无关的其他功能。HDL 辅助蛋白，如对氧磷酶 1（PON1），被认为赋予了 HDL 抗氧化和抗炎特性，并有助于脂蛋白的抗动脉粥样硬化功能。我们旨在评估 HDL-C 水平的极端波动是否与 PON1 活性相关。
在原发性高脂蛋白血症（HAL，HDL-C>90 百分位）、低脂蛋白血症（HA，HDL-C<10 百分位）和对照组受试者中评估 PON1 相关芳基酯酶和内酯酶的水平。还测定了胆固醇外排能力（CEC）通过几种途径和其他代谢参数以及血管疾病的标志物。
尽管 HDL-C 和载脂蛋白 A1（APO A1）发生了明显变化（所有比较均 p<0.001），但与 HA 受试者相比，HAL 受试者的芳基酯酶和内酯酶仅略有增加（p<0.05），但与对照组相比则没有增加。在调整 HDL-C 或 APO A1 后，PON1 活性的这种变化不再显著。两种酶活性仅与水性扩散 CEC 呈正相关（r=0.318，p<0.05 和 r=0.355，p<0.05），与斑块的存在呈负相关（p<0.05）。
我们表明，极端高/低 HDL-C 水平与 PON1 活性的同等增加/减少无关。该酶似乎有助于 HDL 在胆固醇逆转运和抗动脉粥样硬化过程中的作用。需要进一步的研究来证实我们的发现。
