Low Very low-Density Lipoprotein Cholesterol but High Very low-Density Lipoprotein Receptor mRNA Expression in Peripheral White Blood Cells: An Atherogenic Phenotype for Atherosclerosis in a Community-Based Population

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.