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  • Avβ3 single-stranded DNA aptamer attenuates vascular restenosis via Ras-PI3K/MAPK pathway in rats after percutaneous transluminal coronary angioplasty.

Avβ3 single-stranded DNA aptamer attenuates vascular restenosis via Ras-PI3K/MAPK pathway in rats after percutaneous transluminal coronary angioplasty.

Artificial organs (2019-12-28)
Hong-Bing Wu, Zhi-Wei Wang, Feng Shi, Zong-Li Ren, Luo-Cheng Li, Xiao-Ping Hu, Rui Hu, Bo-Wen Li
ABSTRACT

Our aim was to investigate the effect of avβ3 single-stranded DNA aptamer (avβ3 ssDNA) on vascular restenosis in rats after percutaneous transluminal coronary angioplasty (PTCA) via the Ras-PI3K/MAPK pathway. Sixty Sprague-Dawley rats were randomly divided into six groups: sham-operated, PTCA, PTCA+cilengitide (18 mg/kg, n = 8), and avβ3 ssDNA treatment at 50, 100, and 200 μg/kg. Hematoxylin-eosin staining was performed to evaluate the successful establishment of the PTCA model and to assess the degree of intimal hyperplasia. Immunofluorescence and in situ hybridization were carried out to observe the level of avβ3. Immunohistochemistry was used to detect the expression of E-cadherin, N-cadherin, α-smooth muscle actin (α-SMA), angiotensin 1 (ANG1), and ANG2. The expression of osteopontin (OPN), focal adhesion kinase (FAK), Ras, mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), signal transducer and activator of transcription 1 (STAT1), and GTPase was observed by the western blot and quantitative reverse transcription polymerase chain reaction. Compared with rats subjected to PTCA only, those treated with avβ3 ssDNA showed significantly decreased vascular occlusion rate (P < .05). The protein expression of avβ3, OPN, p-FAK, ANG2, and E-cadherin was significantly increased by avβ3 ssDNA (P < .05), while the levels of ANG1, α-SMA, N-cadherin Ras, MAPK, PI3K, STAT1, and GTPase were significantly decreased (P < .05). Avβ3 ssDNA reduced the proliferation, migration, epithelial-mesenchymal transition, and vascular remodeling of vascular smooth muscle cells, and the mechanism may be related to the Ras-PI3K/MAPK pathway.

MATERIALS
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Product Description

Sigma-Aldrich
Solketal methacrylate, 50 wt. % in dichloromethane, contains ~280 ppm 4-tert-butylcatechol as inhibitor
Sigma-Aldrich
Anti-PCDH15 antibody produced in rabbit, affinity isolated antibody