Prevention of neointimal formation after angioplasty using tetramethylpyrazine-coated balloon catheters in a rabbit iliac artery model

Abstract

Background: Restenosis remains a clinical problem; drug-coated balloons (DCBs) have demonstrated high efficiency in this situation. DCBs prevent neointimal hyperplasia by inhibiting cell proliferation and migration. Tetramethylpyrazine (TMP) is a traditional Chinese medicine originally isolated from the rhizome of Ligusticum Walliichii, which can inhibit platelet aggregation and smooth muscle cell proliferation. We hypothesized that TMP-coated balloons (TCB) could reduce neointimal hyperplasia through the NF-κB signalling pathway.Methods: Twenty-one New-Zealand White rabbits (2.5-3.0 kg, male) were fed high-fat diets; 36 bilateral iliac artery stenosis models were successfully established by balloon straining. Rabbits were randomly treated with TCB (n=20) or plain balloons (PBA, n=16) (3 died during model construction). Angiographies were recorded at baseline, the immediate period, and 4 weeks later. Animals were euthanized and arteries collected for histological analysis and immunohistochemical staining. Protein expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 of the vessel samples were analyzed using Western blotting.Results: No difference existed in the baseline lesion characteristics or procedural results. Angiographic follow-up was successfully performed on 18 rabbits (TCB: n=20, PBA: n=16), except for 3 deaths related to the operation. Treatment with TCB was superior to that with PBA, with lower late lumen loss (0.45±0.23 vs. 0.84±0.17 mm, P<0.01). Pathological analysis confirmed the efficiency of TCB through decreasing the area stenosis rate compared with PBA (46.48%±8.22% vs. 75.24%±6.10%, P<0.01). As determined by Western blotting, significant reductions occurred in PCNA and NF-κB p65 protein intensity in the TCB group versus the PBA group (all P<0.01). TCB efficiently mitigated restenosis in the rabbit iliac artery model. Conclusions:This study elucidated that TCB could restrain intimal hyperplasia of vessels by inhibiting the activation of the NF-κB pathway to reduce inflammatory response and decrease the rate of cell proliferation through suppressing PCNA expression.