NF-kB affects migration of vascular smooth muscle cells after treatment with heparin and ibrutinib

Abstract

The migration of vascular smooth muscle cells (VSMCs) is one of the most important events in the remodeling of atherosclerosis plaque. The aim of study was to investigate the role of Heparin in the VSMC migration and its association with the NF-kB, collagen 1 and collagen 3 expression levels. Moreover, the incorporation of Heparin was studied in the VSMC cultures including Betulinic acid and Ibrutinib. Twelve cell groups were cultured and treated with the Heparin, Betulinic acid and Ibrutinib based on the viability and toxicity in 24-h and 48-h periods. The gene and protein expression levels were measured by RT-qPCR and western blotting techniques. The VSMC migration was determined by scratch test. In contrast with Ibrutinib (2 μM), Heparin (30 IU) increased significantly (P < 0.05) the NF-kB gene and protein expression levels and the VSMC migration during the exposure periods. Heparin (15 IU and 30 IU) also increased the collagen 1 gene expression level in the 48-h period while Heparin (5 IU and 15 IU) increased the collagen 3 gene expression levels in both periods. Incorporating Heparin into the cultures including Betulinic acid and Ibrutinib affected the collagen 1 and collagen 3 expression levels. The data suggested that the cell migration relates to NF-kB in the VSMCs treated with Heparin and Ibrutinib. Furthermore, the Heparin doses (5 IU and 15 IU) were safe for VSMCs based on the NF-kB, and collagen 3 expression levels.

Keywords

• VSMCs
• Heparin
• NF-kB
• Collagen
• Betulinic acid
• Ibrutinib