Interaction between CRP/oxLDL complex and endothelial cells

C-reactive protein (CRP) and oxidized low-density lipoprotein (oxLDL) play a significant role in the pro-inflammatory response observed in various vascular diseases. CRP has a characteristic cyclic pentameric structure that forms two binding sites known as the A and B faces. The CRP B face can bind five oxidized phosphatidylcholine molecules in oxLDL in the presence of Ca²⁺. However, how CRP/oxLDL complexes are formed, as well as their effect and corresponding receptors on endothelial cells, remains unknown. In the present study, we found that the inhibition of basal endothelial nitric oxide (NO) release by CRP and oxLDL co-incubates is dependent on the ratio of CRP and oxLDL. Specifically, the concentration ratio of CRP to oxLDL ∼1:20 (CRP/oxLDL-1:20) results in the greatest inhibition of endothelial NO secretion. Pretreatment with neutralizing antibodies for CD32, the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), or keratin 1 (KRT1) abolished the effect of CRP/oxLDL-1:20 on NO production. Furthermore, we found that CD32, LOX-1, and KRT1 mediate the cellular uptake of CRP/oxLDL complexes, in which LOX-1 co-localizes with KRT1, but not CD32. These results provide a novel mechanism by which the multifaceted effects of CRP/oxLDL complexes on endothelial cells can be targeted for the treatment of vasculature diseases.