Inhibition of programmed death‐1 decreases neointimal hyperplasia after patch angioplasty

Abstract

Neointimal hyperplasia remains an obstacle after vascular interventions. Programmed death-1 (PD-1) antibody treatment decreases tumor cell proliferation and secretion of inflammatory factors, and several antineoplastic drugs show efficacy against neointimal hyperplasia. We hypothesized that inhibition of PD-1 inhibits neointimal hyperplasia in a rat patch angioplasty model. In a rat aorta patch angioplasty model, four groups were compared: the control group without treatment, a single dose of humanized PD-1 antibody (4 mg/kg) injected immediately after patch angioplasty, PD-1 antibody-coated patches, and BMS-1 (PD-1 inhibitor)-coated patches. Patches were harvested (Day 14) and analyzed. After patch angioplasty, PD-1-positive cells were present. Inhibition of PD-1 using both intraperitoneal injection of humanized PD1 antibody as well as using patches coated with humanized PD1 antibody significantly decreased neointimal thickness (p = 0.0199). There were significantly fewer PD-1 (p = 0.0148), CD3 (p = 0.0072), CD68 (p = 0.0001), CD45 (p = 0.001), and PCNA (p < 0.0001)-positive cells, and PCNA/α-actin dual positive cells (p = 0.0005), in the treated groups. Patches coated with BMS-1 showed similarly decreased neointimal thickness and accumulation of inflammatory cells. Inhibition of PD-1 using PD-1 antibody or its inhibitor BMS-1 can significantly decrease neointimal thickness in vascular patches. Inhibition of the PD-1 pathway may be a promising therapeutic strategy to inhibit neointimal hyperplasia.

The application of tissue-engineered fish swim bladder vascular graft

“…We also showed that cells migrated and infiltrated into the decellularized fish swim bladder patch in a process similar to our previous observations that cells infiltrated into pericardial patches 23 , 38 , polyester patches 29 , decellularized human saphenous vein patches 25 and decellularized rat thoracic aortic patches 26 . Also similar to other biomaterials, there was rapid reendothelialization after patch implantation or tube interposition; there were no patch pseudoaneurysms after aortic patch angioplasty, suggesting the structural strength and biocompatibility with the arterial environment (Fig.…”

“…We tested the application of the decellularized swim bladder without or with rapamycin coating as patches placed into the rat aorta or the IVC 25 , 26 , 28 , 29 . At day 14, the patches were incorporated into the rat aorta and IVC; there were no aneurysms or occlusions.…”

“…Briefly, after washing 3 times with phosphate-buffered saline (PBS; 5 min/wash), the HA-coated samples were immersed into a rapamycin solution (2 mg/mL; Zhaoke, Hefei, China) that was also advance-activated in water-soluble carbodiimide solution (15 min), and incubated at 37 o C for 6 h 44 . Rhodamine conjugation was carried out in a similar fashion 26 …”

“…Previously we showed that pericardial patches can be coated with rapamycin-containing nanoparticles to inhibit neointimal hyperplasia 23 . The decellularized pericardial patch 23 , decellularized human saphenous vein patch 25 , and rat thoracic aorta patch 26 , 27 can also be coated with heparin or PD-1 antibody to decrease neointimal thickness. We hypothesized that decellularized fish swim bladder can serve as a biological vascular graft scaffold and can be surface modified; accordingly, we created swim bladder-derived scaffolds, coated them with rapamycin, shaped them into patches or tubes, and implanted them into rats to determine biocompatibility.…”

Integrin α9 regulates smooth muscle cell phenotype switching and vascular remodeling

“…Antibody or oligonucleotide infusion or viral vectors have been widely used to inhibit the signaling pathways for the prevention of neointimal hyperplasia (32)(33)(34)(35)(36). Next, we evaluated whether injury-induced neointimal hyperplasia could be reduced by blocking α9β1 signaling.…”