Gefitinib-coated balloon inhibits the excessive hyperplasia of intima after vascular injuries through PI3K/AKT pathway

Abstract

OBJECTIVE: To explore the effect of gefitinib-coated balloon suppressive action on the excessive hyperplasia of intima after balloon injury of common carotid artery in rats and on the PI3K/AKT signal pathway. METHODS: MTT method and the expression of Bcl-2 and Caspase-3 proteins were detected in vitro ; Adult SD rats were randomly split into 5 groups, namely sham group, model group, low-dosage gefitinib-coated balloon group, high-dosage gefitinib-coated balloon group, and paclitaxel-coated balloon group. The intimal proliferation of arteries, PCNA, P-AKT and PI3K protein expression, the cell apoptosis, expression of MMP9, TGF and IL6 mRNA were measured by hematoxylin and eosin (H&E) staining, immunohistochemistry, TUNEL staining, and RT-qPCR. RESULTS: At the same time and concentration, Gefitinib suppressed the proliferation of smooth muscle cell more significantly than paclitaxel. Bcl-2 and Caspase-3 in vascular smooth muscle and endothelial cells (VSMC, EC) were significantly down-regulated and up-regulated after the cells were treated with gefitinib and paclitaxel. In gefitinib- and paclitaxel-coated balloon groups, significant up-regulations were found in the area of lumen. Furthermore, the expression of PCNA suggested that all coated balloons could suppress the excessive proliferation of smooth muscle cells in the hyperplastic intima compared with the control group. In gefitinib- and paclitaxel-coated balloon group, the expression of PI3K/AKT was significantly down-regulated. The use of drug-coated balloons mitigated the cell apoptosis in TUNEL. The expressions of MMP9, TGF and IL6 mRNA in the model group were obviously up-regulated; and they were obviously down-regulated in the high-dose gefitinib-coated balloon group compared with the model group. CONCLUSIONS: Gefitinib-coated balloons were able to suppress the excessive proliferation in the common carotid arterial intima of rats more effectively than the paclitaxel-coated ones. The underlying mechanism may cover the PI3K/AKT signal pathway.

Hydroxysafflor Yellow A inhibits the viability and migration of vascular smooth muscle cells induced by serum from rats with chronic renal failure via inactivation of the PI3K/Akt signaling pathway

“…However, high concentrations of CRF serum also increase cell apoptosis, which may be due to toxicants in the serum that disrupt cell survival. Activation of the PI3K/Akt signaling pathway is closely associated with aberrant viability and migration of VSMCs ( 11 , 12 , 39 ). In addition, activation of the PI3K/Akt signaling pathway has been observed in mice with renal dysfunction caused by ischemia/reperfusion-injury ( 40 , 41 ).…”

The effect of endothelial progenitor cell transplantation on neointimal hyperplasia and reendothelialisation after balloon catheter injury in rat carotid arteries

“…We aimed to determine the reendothelialisation after BI using 3D evaluation. The distribution of transplanted EPCs changes in 3D over time, but the impairment of endothelial integrity was typically measured with cross-sections or longitudinal sections and subsequent histological analysis [27][28][29]. Transplanted EPCs labelled with PKH26 could be observed in the 551-nm channel under a light-sheet microscope and attached to the luminal surface of BI arteries on the first day.…”

Preventive Effect and Mechanism of Crossostephium chinense Extract on Balloon Angioplasty-Induced Neointimal Hyperplasia

“…The PI3K-AKT-mTOR pathway, a crucial downstream cascade of PDGFRs, participated in PDGF-mediated physiological and pathological regulation [ 25 , 26 ]. Inhibiting PDGFRs or targeting the PI3K-AKT pathway could alleviate excessive neointimal hyperplasia [ 27 , 28 ]. MMP2, a gelatinase that can digest the extracellular matrix, was increased in the balloon-injured arteries of the hypercholesterolemic rabbit [ 29 ], and neutralizing MMP2 activity could inhibit VSMC migration [ 30 ].…”