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

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

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

high-density lipoproteinangiogenesisautophagyATG5miRNAendothelial nitric oxide synthase

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

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Division of Cardiac Surgery,Cardiovascular Diseases Institute,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China

National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases,Guangzhou 510080,China

NHC key Laboratory of Assisted Circulation(Sun Yat-sen University),Guangzhou 510080,China

Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases,Guangzhou 510080,China

Division of Vascular Surgery,The Firs

Department of Pharmacology,Cardiac and Cerebral Vascular Research Center,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou 510080,China

Division of Hypertension and Vascular Diseases,Department of Cardiology,Cardiovascular Diseases Institute,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080

Guangdong Provincial Key Laboratory o

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaGuangdong Basic and Applied Basic Research FoundationScience and Technology Planning Project of Guangzhou,ChinaSun Yatsen University Clinical Research 5010 ProgramProgram of National Key Clinical Specialties

8183001382100424.92268202.819703632021YFA08051002019B15151200922021030000162014002

2024

10.1007/s11427-022-2381-7

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(2)
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