High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p

作     者：Bi-Ang Kang Hua-Ming Li Ya-Ting Chen Meng-Jie Deng Yan Li Yue-Ming Peng Jian-Jun Gao Zhi-Wei Mo Jia-Guo Zhou Zhi-Jun Ou Jing-Song Ou 

作者机构：Division of Cardiac SurgeryCardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular DiseasesGuangzhou 510080China NHC key Laboratory of Assisted Circulation(Sun Yat-sen University)Guangzhou 510080China Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular DiseasesGuangzhou 510080China Division of Vascular SurgeryThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of PharmacologyCardiac and Cerebral Vascular Research CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Division of Hypertension and Vascular DiseasesDepartment of CardiologyCardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Brain Function and DiseaseZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2024年第67卷第2期

页      面：286-300页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(81830013,82100424,92268202,81970363) the National Key Research and Development Program of China(2021YFA0805100) Guangdong Basic and Applied Basic Research Foundation(2019B1515120092) Science and Technology Planning Project of Guangzhou China(202103000016) the Sun Yat-sen University Clinical Research 5010 Program(2014002) Program of National Key Clinical Specialties 

主　　题：high-density lipoprotein angiogenesis autophagy ATG5 miRNA endothelial nitric oxide synthase 

摘      要：We previously demonstrated that normal high-density lipoprotein(nHDL)can promote angiogenesis,whereas HDL from patients with coronary artery disease(d HDL)is dysfunctional and impairs *** plays a critical role in angiogenesis,and HDL regulates ***,it is unclear whether n HDL and d HDL regulate angiogenesis by affecting *** cells(ECs)were treated with n HDL and d HDL with or without an autophagy ***,endothelial nitric oxide synthase(e NOS)expression,miRNA expression,nitric oxide(NO)production,superoxide anion(O2^(·-))generation,EC migration,and tube formation were evaluated.n HDL suppressed the expression of miR-181a-5p,which promotes autophagy and the expression of e NOS,resulting in NO production and the inhibition of O2^(·-)generation,and ultimately increasing in EC migration and tube formation.d HDL showed opposite effects compared to n HDL and ultimately inhibited EC migration and tube *** found that autophagy-related protein 5(ATG5)was a direct target of ***5 silencing or miR-181a-5p mimic inhibited n HDL-induced autophagy,e NOS expression,NO production,EC migration,tube formation,and enhanced O2^(·-)generation,whereas overexpression of ATG5 or miR-181a-5p inhibitor reversed the above effects of d ***5 expression and angiogenesis were decreased in the ischemic lower limbs of hypercholesterolemic low-density lipoprotein receptor null(LDLr^(-/-))mice when compared to C57BL/6 ***5 overexpression improved angiogenesis in ischemic hypercholesterolemic LDLr^(-/-)*** together,nHDL was able to stimulate autophagy by suppressing miR-181a-5p,subsequently increasing e NOS expression,which generated NO and promoted *** contrast,d HDL inhibited angiogenesis,at least partially,by increasing miR-181a-5p expression,which decreased autophagy and e NOS expression,resulting in a decrease in NO production and an increase in O2^(·-)*** findings reveal a nov