Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
EBioMedicine. 2017 Nov;25:136-142. doi: 10.1016/j.ebiom.2017.08.019. Epub 2017 Aug 31.
Very low-density lipoprotein cholesterol (VLDL-C), via binding very low-density lipoprotein receptor (VLDLR), can induce the development of atherosclerosis. Besides monocytes, VLDLR expression is detected in various peripheral white blood cells (WBCs), yet its underlying role remains unclear. We thereby aimed to test the hypothesis that VLDLR in all types of peripheral WBCs may be involved in the association between VLDL-C and atherosclerosis. VLDLR mRNA expression in peripheral WBC and plasma VLDL-C levels were measured in 747 participants from a community-based study. Plaque prevalence and total plaque area (TPA) were used to evaluate the burden of carotid atherosclerosis. VLDL-C was positively associated with atherosclerosis risk, whereas this association was modified by VLDLR mRNA level. In participants with the lowest VLDL-C but the highest VLDLR mRNA expression, the risk for plaque prevalence unexpectedly was the highest. This association was also observed for TPA. Moreover, this association remained unchanged after adjusting for WBC or monocytes. Our findings described an atherogenic phenotype characterized by low VLDL-C but high VLDLR mRNA expression in peripheral WBCs, which suggested that VLDLR in all types of peripheral WBCs may be involved in lipid deposition, and VLDL-C and VLDLR may co-determine the development of atherosclerosis.
极低密度脂蛋白胆固醇 (VLDL-C) 通过与极低密度脂蛋白受体 (VLDLR) 结合,可诱导动脉粥样硬化的发生。除单核细胞外,VLDLR 在各种外周白细胞 (WBC) 中也有表达,但作用机制尚不清楚。因此,我们旨在检验以下假说,即所有类型的外周 WBC 中的 VLDLR 可能参与了 VLDL-C 与动脉粥样硬化之间的关联。我们在一项基于社区的研究中,对 747 名参与者的外周 WBC 中的 VLDLR mRNA 表达和血浆 VLDL-C 水平进行了测量。斑块发生率和总斑块面积 (TPA) 用于评估颈动脉粥样硬化的负担。VLDL-C 与动脉粥样硬化风险呈正相关,而这种关联受到 VLDLR mRNA 水平的修饰。在 VLDL-C 最低但 VLDLR mRNA 表达最高的参与者中,斑块发生率的风险出乎意料地最高。这种关联也存在于 TPA 中。此外,在调整了 WBC 或单核细胞后,这种关联仍然不变。我们的研究结果描述了一种动脉粥样硬化表型,其特征是外周 WBC 中 VLDL-C 低但 VLDLR mRNA 表达高,这表明所有类型的外周 WBC 中的 VLDLR 可能参与脂质沉积,VLDL-C 和 VLDLR 可能共同决定动脉粥样硬化的发生。