Hispolon Attenuates Balloon-Injured Neointimal Formation and Modulates Vascular Smooth Muscle Cell Migration via AKT and ERK Phosphorylation

Abstract

The pathological mechanism of restenosis is attributed primarily to excessive proliferation and migration of vascular smooth muscle cells (VSMC). The preventive effects of hispolon (1) on balloon injury-induced neointimal formation were investigated, and 1 showed potent activity in inhibiting fetal bovine serum-induced VSMC outgrowth. Hispolon (1) significantly inhibited VSMC migration, as shown by trans-well assays. Compound 1 decreased the expression and secretion of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The expression of the endogenous inhibitors of these proteins, namely, tissue inhibitors of MMP (TIMP-1 and TIMP-2), increased. The inhibition by noncytotoxic doses of 1 of VSMC migration was through its negative regulatory effects on FAK phosphorylation, ERK1/2 phosphorylation, and PI3K/AKT. These results demonstrate that 1 can inhibit the migration of VSMC by reduced expression of MMP-9 through the suppression of the FAK signaling pathway and of the activity of PI3K/AKT. The data obtained suggest that 1 might block balloon injury-induced neointimal hyperplasia via the inhibition of VSMC proliferation and migration, without inducing apoptosis.

Deep Sea Water Prevents Balloon Angioplasty-Induced Hyperplasia through MMP-2: An In Vitro and In Vivo Study

“…The rats were given DSW for 4 weeks and performance angioplasty during the second week. Balloon injury-induced neointimal hyperplasia was carried out using a balloon embolectomy catheter as described previously [13] A Fogarty 2F (Becton-Dickinson, Franklin Lakes, NJ, USA) embolectomy balloon catheter was inserted into the left external carotid artery and inflated under the same pressure (1.3kg/cm 2 ) for three consecutive three times. All animal care followed the institutional animal ethical guidelines of China Medical University.…”

Demethoxycurcumin, a major active curcuminoid from Curcuma longa, suppresses balloon injury induced vascular smooth muscle cell migration and neointima formation: An in vitro and in vivo study

“…The effects of curcuminoids on the viability of VSMCs were monitored using a modified MTT assay . Briefly, cells were seeded into 96‐well plates (8 × 10 3 cells/well) and maintained in DMEM containing 15% FBS.…”

“…As described previously , VSMCs (2.7 × 10 5 cells/well) were incubated with curcumin, DMC, or BDMC for 24 h. The cells were then fixed with 70% ethanol overnight, treated with 20 μg/mL RNase (Sigma Chemical Co.), and stained with 0.5 mg/mL propidium iodide (Santa Cruz Biotechnology Co.). DNA content was determined using a FACS can flow cytometer (Becton Dickinson, San Jose, CA, USA) and analyzed using the DNA analysis software program ModFitLT, version 2.0 (Verity Software, Topsham, ME, USA).…”

Suppressive activities and mechanisms of ugonin J on vascular smooth muscle cells and balloon angioplasty‐induced neointimal hyperplasia

“…Rats were randomly divided into three groups ( n = 9/group), including sham control, balloon injury (BI), and BI + ugonin J groups. Surgery was performed under Zoletil® anesthesia (50 mg/kg; intraperitoneal injection), and angioplasty of the carotid artery was performed using a balloon embolectomy catheter, as described previously (Chien, Huang, Cheng, Wu, & Sheu, ). The balloon catheter (2F Fogarty; Becton‐Dickinson, Franklin Lakes, NJ, USA) was introduced through the left external carotid artery into the common carotid artery, and the balloon was inflated at 1.3 kg/cm 2 using an inflation device.…”