622-P: Mechanism of Lin28a Promoting Vascular Smooth Muscle Cell Proliferation and Migration in Restenosis

Abstract

Background: Restenosis (RS) after percutaneous transluminal angioplasty severely affects the curative effect of patients with lower extremity peripheral arterial disease. Our previous research indicated that abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) was the key factor in the RS plaque formation. The process of Lin28a regulating cell proliferation demonstrates similarities with the proliferation of VSMCs in RS. Here, we aim to explore the specific role of Lin28a in RS. Methods: To distinguish from atherosclerotic lesions, RS and atherosclerosis (AS) models were simultaneously established in type 2 diabetic rats. Lin28a level in VSMCs was detected by immunofluorescence double staining. The changes of VSMCs were determined when modulating Lin28a in vivo and vitro and downstream mechanism was further explored. Results: Thirty-two folds higher level of Lin28a was found in VSMCs in RS compared with AS (P Conclusion: The present study demonstrated that Lin28a is critically involved in the progression of RS via facilitating the proliferation and migration of VSMCs. A double negative feedback loop is often present in Let7 and Lin28a, thus Let7 subtypes were detected and Let7c could be the direct downstream of Lin28a in regulating VSMCs in RS. Combined with the fact that Lin28a was also regulated by Let7c, we inferred a feedback loop could be formed between Let7c and Lin28a. Above all, the interaction in Lin28a and Let7c may contribute to rapid formation of RS. Disclosure Q. Zhang: None. X. Zhou: None. X. Shen: None. S. Jiang: None. T. Xie: None. Z. Zou: None. C. Xu: None. R. Zhang: None. Y. Cui: None. P. Gong: None. J. Dong: None. L. Liao: None. Funding National Natural Science Foundation of China (81670757, 81570742, 81770822, 81800732); Shandong Provincial Natural Science Foundation of China (ZR2017LH025); Shandong Provincial Medicine and Health Science and Technology Development Program (2017WS461)