title: Modified VEGF targets the ischemic myocardium and promotes functional recovery after myocardial infarction.
abstract: Vascular endothelial growth factor (VEGF) promotes angiogenesis and improves cardiac function after myocardial infarction (MI). However, the non-targeted delivery of VEGF decreases its therapeutic efficacy due to an insufficient local concentration in the ischemic myocardium. In this study, we used a specific peptide to modify VEGF and determined that this modified VEGF (IMT-VEGF) localized to the ischemic myocardium through intravenous injection by interacting with cardiac troponin I (cTnI). When IMT-VEGF was used to mediate cardiac repair in a rat model of ischemia-reperfusion (I-R) injury, we observed a decreased scar size, enhanced angiogenesis and improved cardiac function. Moreover, an alternative treatment using the repeated administration of a low-dose IMT-VEGF also promoted angiogenesis and functional recovery. The therapeutic effects of IMT-VEGF were further confirmed in a pig model of MI as the result of the conserved properties of its interacting protein, cTnI. These results suggest a promising therapeutic strategy for MI based on the targeted delivery of IMT-VEGF.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing, 100190, China; Graduate School, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing, 100190, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing, 100190, China; Institute for Translational Medicine, College of Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266021, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing, 100190, China; Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing, 100190, China; Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing, 100190, China; Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, 398 Ruoshui Road, Suzhou, 215123, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tan
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, 398 Ruoshui Road, Suzhou, 215123, China.
authors.forename: Zongwu
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Cardiothoracic Surgery, the affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, China.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Cardiac Surgery, Peking Union Medical College Hospital, Peking Union Medical College, 1 Shuaifuyuan, Beijing, 100730, China.
authors.forename: Jianzhou
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing, 100190, China; Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Cardiac Surgery, Peking Union Medical College Hospital, Peking Union Medical College, 1 Shuaifuyuan, Beijing, 100730, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Miao
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing, 100190, China; Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Road, Chongqing, 400038, China. Electronic address: jwdai@genetics.ac.cn.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006321:Heart / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D010455:Peptides; D042461:Vascular Endothelial Growth Factor A
keywords: Drug delivery; Myocardial infarction; Targeting therapy; VEGF