Chemokine-like factor 1 (CKLF1) aggravates neointimal hyperplasia through activating the NF-κB /VCAM-1 pathway

Abstract

Neointimal hyperplasia (NIH) is a complicated inflammatory process contributing to vascular restenosis. The present study aimed to explore whether chemokine-like factor 1 (CKLF1) aggravates NIH via the nuclear factor-kappa B (NF-κB)/vascular cell adhesion molecule-1 (VCAM-1) pathway. We found the expression of CKLF1 and VCAM-1 significantly increased in human carotid plaques compared to the control. In vivo, CKLF1 overexpression induced a thicker neointimal formation and VCAM-1 expression was correspondingly upregulated. In vitro, CKLF1 activated NF-κB and induced VCAM-1 upregulation in human aortic smooth muscle cells (HASMCs). Functional experiments demonstrated that CKLF1 promoted monocyte adhesion and HASMC migration via VCAM-1. These results suggest CKLF1 accelerates NIH by promoting monocyte adhesion and HASMC migration via the NF-κB/VCAM-1 pathway. Our findings contribute to a better understanding of the mechanisms underlying the causality of CKLF1 on NIH and could prove beneficial in designing therapeutic modalities with a focus on CKLF1.

Keywords: NF-κB; VCAM-1; chemokine-like factor 1; neointimal hyperplasia; restenosis.