Keratin-1 is a novel binding protein for C-reactive protein on the membrane of endothelial cells

Abstract

C-reactive protein (CRP) is a sensitive marker of systemic inflammation. Recent investigations have shown that CRP correlates with cardiovascular disease and endothelial dysfunction. CRP exerts its effects on endothelial cells through binding to its receptors, CD32 and the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). As an acute-phase protein, CRP is capable of binding to various molecules and may bind to the receptor other than CD32 and LOX-1. Here, we identified keratin-1 (KRT1) on endothelial cells as a novel protein for CRP binding by affinity chromatography and mass spectrometry. The interaction between KRT1 and CRP was also confirmed by the antibody blockade of KRT1 that decreased the CRP uptake and blocked CRP-mediated reduction in nitric oxide (NO) release in human aortic endothelial cells (HAECs). Additionally, a reduced KRT1 expression by KRT1 small hairpin RNAs increased NO release in the presence of CRP.