Immune Mechanisms of Extracellular Matrix Remodeling in the Common Carotid: A Model of Intimal Hyperplasia

Abstract

Intimal hyperplasia (IH) is characteristic of a cell population increase within the innermost layer of the arterial wall. It is hypothesized that extracellular matrix vascular remodeling secondary vascular injury is dependent upon the Th17 subset of the CD4+ lymphocytes. Male C57BL/6J and FVB/NJ murine strains underwent complete left common carotid artery ligation for periods of 14 and 28 days. A therapeutic simvastatin model was carried out in the FVB/NJ strain and involved a daily subcutaneous injection regimen of 40 mg/kg/mouse beginning 72 hours prior to and daily following a 14 day carotid ligation period. Histological and RT-PCR analysis was carried out with harvested carotid artery samples. The FVB/NJ 14 day and 28 day histological stains of the left common carotid artery following ligation injury developed evident structured and disassembled intimal hyperplasia, respectively. A gene array demonstrated dramatic expression of immune and cytokine transcription markers particularly in the FVB/NJ strain at both ligation time points. IL-17 and IL-6 transcriptional gene expression was upregulated greater than 20-fold in the FVB/NJ 28 day injury model. IL-17 transcription was significantly expressed by a change of 50.06 ± 0.19 (p = 0.004) in this strain at 28 days versus the control. Lastly, the simvastatin treatment model was found to exacerbate the immune response to ligation injury. These results revealed that the immune system elicits a role in the vascular remodeling that potentiates intimal hyperplasia.