Hyperglycemia has no effect on development of restenosis after percutaneous transluminal angioplasty (PTA) in a diabetic rabbit model

J Cellular Molecular Medi

Zhang

et al. 2020

Self Cite

To explore the potential role of Lin28a in the development of restenosis after percutaneous transluminal angioplasty, double‐balloon injury surgery and mono‐balloon injury surgery were used to establish restenosis and atherosclerosis models, respectively, so as to better distinguish restenosis from atherosclerotic lesions. Immunohistochemical analysis revealed that significantly higher expression of Lin28a was observed in the iliac arteries of restenosis plaques than that of atherosclerosis plaques. Immunofluorescence studies showed the colocalization of Lin28a with α‐smooth muscle actin in restenosis plaques, rather than in atherosclerosis plaques, which suggested that Lin28a might be related to the unique behaviour of vascular smooth muscle cells (VSMCs) in restenosis. To further confirm above hypothesis, Lin28a expression was up‐regulated by transfection of Lenti‐Lin28a and inhibited by Lenti‐Lin28a‐shRNA transfection in cultured VSMCs, and then the proliferation and migration capability of VSMCs were detected by EdU and Transwell assays, respectively. Results showed that the proliferation and migration of VSMCs were significantly increased in accordance with the up‐regulation of Lin28a expression, while above behaviours of VSMCs were significantly suppressed after inhibiting the expression of Lin28a. In conclusion, the up‐regulation of Lin28a exerts its modulatory effect on VSMCs’ proliferation and migration, which may play a critical role in contributing to pathological formation of restenosis.

Section: Discussionsupporting

confidence: 84%

Section: Methodsmentioning

confidence: 99%

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Lin28a up‐regulation is associated with the formation of restenosis via promoting proliferation and migration of vascular smooth muscle cells

Zou

J Cellular Molecular Medi

Zhang

et al. 2020

Self Cite

“…Induction of experimental diabetes mellitus: after an overnight fasting, 80 mg/kg of freshly prepared alloxan solution was injected intravenously from the marginal ear vein of rabbits [ 10 ]. Animals had free access to food and water after the alloxan injection, and an oral solution of 20 % glucose was provided after confirmation of hypoglycemia to prevent hypoglycemic shock.…”

Section: Methodsmentioning

confidence: 99%

“…One week after diabetes induction, rabbits were anesthetized with phenobarbital. An arteriotomy in the right saphenous artery was made with standard surgical techniques, then a 2.5-mm, wire-guided balloon catheter was inserted and the iliac artery injury was made as previously described [ 10 ] (Fig. 1a ).…”

Section: Methodsmentioning

confidence: 99%

The role of atorvastatin on the restenosis process post-PTA in a diabetic rabbit model

Mou

Shen

et al. 2016

BMC Cardiovasc Disord

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BackgroundRestenosis remains to be a major limitation of percutaneous transluminal angioplasty (PTA) for diabetic patients with peripheral vascular disease (PVD). Despite of stations routine implements to prevent such progress, its exact effect is unclear.Methods and resultsIn our study, balloon was successfully implanted in the iliac artery of atherosclerotic rabbit. Patency of the narrowed artery was interrogated using ultrasound. Atorvastatin or vehicle was administered orally to rabbits from day 0 to day 28 after double-injury surgery. On day 7, day 14, and day 28, restenotic arteries were harvested and processed for histopathlogical analysis. Our data show that, after double-injury surgery, the intima was composed mostly by SMCs at all time course in rabbits undergoing surgery process. Significant increases in stenosis rates were noted from day 7 to day 14 (from 21 ± 5.85 % to 60.93 ± 12.46 %). On day 28 after double-injury surgery, severe restenosis was observed and daily administration of atorvastatin cannot prevent restenosis’ formation (88.69 ± 3.71 % vs. 90.02 ± 3.11 %, P > 0.05). The PCNA index and SMCs proliferation were correlated with the scores of the vascular pathology.ConclusionsOur results indicate that double-injury model can mimic clinical restenosis, based on this model, atorvastatin showed no therapeutic effect on restenosis process in diabetic rabbits after PTA.

Effect of down-regulation of let-7c/g on triggering a double-negative feedback loop and promoting restenosis

Zhang

Chinese Medical Journal

et al. 2023

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Background: Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are the main cause of restenosis (RS) in diabetic lower extremity arterial disease (LEAD). However, the relevant pathogenic mechanisms are poorly understood. Methods: In this study, we introduced a "two-step injury protocol" rat RS model, which started with the induction of atherosclerosis (AS) and was followed by percutaneous transluminal angioplasty (PTA). Hematoxylin-eosin (HE) staining and immunohistochemistry staining were used to verify the form of RS. Two-step transfection was performed, with the first transfection of Lin28a followed by a second transfection of let-7c and let-7g, to explore the possible mechanism by which Lin28a exerted effects. 5-ethynyl-2΄-deoxyuridine (EdU) and Transwell assay were performed to evaluate the ability of proliferation and migration of VSMCs. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the expression of Lin28a protein and let-7 family members. Results: Using a combination of in vitro and in vivo experiments, we discovered that let-7c, let-7g, and microRNA98 (miR98) were downstream targets of Lin28a. More importantly, decreased expression of let-7c/let-7g increased Lin28a, leading to further inhibition of let-7c/let-7g. We also found an increased level of let-7d in the RS pathological condition, suggesting that it may function as a protective regulator of the Lin28a/let-7 loop by inhibiting the proliferation and migration of VSMCs. Conclusion: These findings indicated the presence of a double-negative feedback loop consisting of Lin28a and let-7c/let-7g, which may be responsible for the vicious behavior of VSMCs in RS.