Vaspin alleviates the lncRNA LEF1-AS1-induced osteogenic differentiation of vascular smooth muscle cells via the Hippo/YAP signaling pathway.

Vascular calcification (VC) is closely related to higher cardiovascular mortality and morbidity, and vascular smooth muscle cell (VSMC) switching to osteogenic-like cells is crucial for VC. LncRNA LEF1-AS1 promotes atherosclerosis and dental pulp stem cells calcification, while its role in VC remains unknown. Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine regulating bone metabolism. However, the relationship between vaspin and VC is still unclear. We aimed to explore the role of LEF1-AS1 on VSMC osteogenic transition, whether vaspin inhibited LEF1-AS1-mediated osteogenic differentiation of VSMCs, and the responsible mechanism. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis indicated that LEF1-AS1 overexpression significantly upregulated osteogenic marker Runt-related transcription factor-2 (RUNX2) level and downregulated VSMC contractile marker α-smooth muscle actin (α-SMA) level. Alizarin red staining, alkaline phosphatase (ALP) staining, ALP activity assay, and calcium content assay also suggested that LEF1-AS1 overexpression promoted calcium deposition in VSMCs. However, vaspin treatment abolished this phenomenon. Mechanistically, LEF1-AS1 markedly decreased phosphorylated YAP level, while vaspin reversed LEF1-AS1-induced phosphorylated YAP decline. Our results revealed that LEF1-AS1 accelerated the osteogenic differentiation of VSMCs by regulating the Hippo/YAP pathway, while vaspin eliminated the LEF1-AS1-meditated VSMCs osteogenic phenotype switch.

Cutting balloon combined with paclitaxel-eluting balloon for treatment of in-stent restenosis.

BACKGROUND: The optimal therapy for in-stent restenosis (ISR) is controversial. We evaluated three different strategies for the treatment of in-stent restenosis: cutting balloon angioplasty (CBA), paclitaxel-eluting balloon angioplasty (PEBA) and cutting balloon followed by paclitaxel-eluting balloon angioplasty (CB+PEBA). METHODS: Forty-five coronary arteries in 45 mini-pigs underwent oversized bare-metal stent (stent-to-artery ratio, 1.2:1) implantation to induce in-stent restenosis. After 28 days, vessels with in-stent restenosis (≥50% diameter stenosis) were randomly divided into three groups: CBA, PEBA and CB+PEBA. In vivo angiography was performed before intervention, immediately after intervention and at 28-day follow-up. Stented arteries were harvested for pathological analyses. The proliferation and apoptosis of vascular smooth muscle cells were evaluated by immunohistochemical staining and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, respectively. RESULTS: Acute lumen gain was not different between the three groups. Late lumen loss and neointimal area at follow-up were lower for CB+PEBA compared with CBA but similar for CB+PEBA compared with PEBA. There were no significant differences in proliferating cell nuclear antigen-positive vascular smooth muscle cells and TUNEL-positive vascular smooth muscle cells between the CB+PEBA and PEBA groups. CONCLUSIONS: PEBA with or without cutting balloon was superior to CBA alone for in-stent restenosis. The underlying mechanism was probably related to inhibition of smooth muscle cell proliferation and increased apoptosis. In this porcine coronary artery restenosis model, PEBA with or without cutting balloon was superior.

Optical coherence tomographic observations of polytetrafluoroethylene-covered sirolimus-eluting coronary arterial stent.

The aim of this study was to evaluate neointimal coverage obtained using a new method of polytetrafluoroethylene-covered stent (PCS) implantation combined with underlying longer sirolimus-eluting stent (SES) implantation using optical coherence tomography. Nine patients were enrolled in this study, including patients with coronary artery perforations, original coronary aneurysms, and acquired coronary aneurysms after drug-eluting stent implantation. All patients were first treated with long SES implantation and then with focal PCS implantation. Postprocedural and follow-up angiographic and optical coherence tomographic examinations were performed in all patients, and intravascular ultrasound was performed in 5 patients. All patients were asymptomatic during follow-up, without recurrent angina. There was no stent-edge or stent-segment binary restenosis. Values of late loss for proximal SES segments, PCS segments, and distal SES segments were similar (0.09, 0.07, and 0.04 mm, respectively, p = 0.8113). The mean neointimal thickness of PCS was less than that of proximal and distal SES. However, no malapposed cross sections or uncovered cross sections were found in PCS segments compared with SES segments (p = 0.0011). In conclusion, the combination of PCS and underlying longer SES implantation can offer better angiographic follow-up results. High-resolution optical coherence tomography provided convincing proof of full neointimal coverage of PCS. This new method of combined PCS and SES implantation may be a better choice compared with direct PCS implantation in certain clinical settings.

A novel polymer-free paclitaxel-eluting stent with a nanoporous surface for rapid endothelialization and inhibition of intimal hyperplasia: Comparison with a polymer-based sirolimus-eluting stent and bare metal stent in a porcine model.

Hypersensitivity and inflammatory responses to polymers may be responsible for late stent thrombosis after implantation of a drug-eluting stent (DES). Polymer-free DES may reduce the prevalence of these adverse reactions in vessels. We evaluated a polymer-free paclitaxel-eluting-stent with a nanoporous surface (nano-PES) for endothelialization and inhibition of neointimal hyperplasia by optical coherence tomography (OCT) and pathology in a porcine model. Nano-PES with high-dose (HD) and low-dose (LD) paclitaxel (1.0 µg/mm(2) and 0.4 µg/mm(2), respectively) was compared with a sirolimus-eluting stent (SES) and bare-metal stent (BMS) in a porcine model. Fifty-three stents (14 HD, 14 LD, 14 SES, 11 BMS) were implanted in 18 minipigs. At 14 days, nano-PES with HD and LD showed more complete endothelialization compared with SES. BMS had 100% endothelial coverage. At 28 days, a significant reduction in neointimal hyperplasia was detected by OCT in the nano-PES HD group compared with BMS. No benefit in prevention of the neointimal hyperplasia was observed in the nano-PES LD group. Nano-PES stents showed decreased deposition of fibrin and inflammation compared with SES. Pharmacokinetic studies revealed that nano-PES could effectively deliver the drug to the local coronary artery and it released the drug more rapidly than SES. Such a release profile was favorable for rapid endothelialization of nano-PES. The present study showed the nano-PES to be a new drug-delivery technology; that it used a nanoporous stent surface; that it offered desirable drug-elution properties without the use of polymers; that it may translate into an improved safety profile for next-generation DES.