Inhibition of heat shock protein 90 attenuates post‑angioplasty intimal hyperplasia

Abstract

intimal hyperplasia (iH) is a pathologic process that leads to restenosis after treatment for peripheral arterial disease. Heat shock protein 90 (HSP90) is a molecular chaperone that regulates protein maturation. activation of HSP90 results in increased cell migration and proliferation. 17-n-allylamino-17-demethoxygeldanamycin (17-aaG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-dMaG) are low toxicity Food and drug association approved HSP90 inhibitors. The current study hypothesized that HSP90 inhibition was predicted to reduce vascular smooth muscle cell (VSMc) migration and proliferation. in addition, localized HSP90 inhibition may inhibit post-angioplasty iH formation. For proliferation, VSMcs were treated with serum-free media (SFM), 17-dMaG or 17-aaG. The selected proliferative agents were SFM, platelet derived growth factor (PDGF) or fibronectin. After three days, proliferation was measured. For migration, VSMcs were treated with SFM, 17-aaG or 17-dMaG with SFM, PdGF or fibronectin as chemoattractants. Balloon injury to the carotid artery was performed in rats. The groups included in the present study were the control, saline control, 17-dMaG in 20% pluronic gel delivered topically to the adventitia or intraluminal delivery of 17-DMAG. After 14 days, arteries were fixed and sectioned for morphometric analysis. data was analyzed using anoVa or a student's t-test. P<0.05 was considered to indicate a statistically significant difference. The results revealed that 17-AAG and 17-dMaG had no effect on cell viability. PdGF and fibronectin also increased VSMC proliferation and migration. Furthermore, both 17-aaG and 17-dMaG decreased cell migration and proliferation in all agonists. Topical adventitial treatment with 17-dMaG after balloon arterial injury reduced iH. HSP90 inhibitors suppressed VSMc proliferation and migration without affecting cell viability. Topical treatment with a HSP90 inhibitor (dMaG) decreased iH formation after arterial injury. it was concluded that 17-dMaG may be utilized as an effective therapy to prevent restenosis after revascularization.

Extracellular vesicles produced by human-induced pluripotent stem cell-derived endothelial cells can prevent arterial stenosis in mice via autophagy regulation

“…Arterial restenosis represents a major complication in vascular reconstructive procedures, such as balloon angioplasty, bypass grafting, stent angioplasty, and endarterectomy. Stimuli, such as an altered blood flow, mechanical load, and vascular endothelial injury in the postoperative period, followed by recruitment and infiltration of inflammatory cells into the vascular walls and subsequent secretion of cytokines and growth factors lead to the vascular smooth muscle cell (VSMC) proliferation and migration, and result in IH, which further progresses into vascular restenosis (1)(2)(3)(4). Therefore, the exploration of effective strategies for IH intervention is necessary to prevent postoperative restenosis.…”