title: Intramyocardial Injection of Recombinant Adeno-Associated Viral Vector Coexpressing PR39/Adrenomedullin Enhances Angiogenesis and Reduces Apoptosis in a Rat Myocardial Infarction Model.
abstract: Cotransfer of angiogenic and antiapoptotic genes could be the basis of new gene therapy strategies for myocardial infarction. In this study, rAAV-PR39-ADM, coexpressing antimicrobial peptide (PR39) and adrenomedullin (ADM), was designed with the mediation of recombinant adeno-associated virus. In vitro, CRL-1730 cells were divided into four groups, namely, the sham group, the AAV-null group, the NS (normal saline) group, and the PR39-ADM group. Immunocytochemistry analysis, CCK-8 assays, Matrigel assays, and apoptotic analysis were performed; in vivo, myocardial infarction model was established through ligation of the left coronary artery on rats, and treatment groups corresponded to those used in vitro. Myocardial injury, cardiac performance, and the extent of myocardial apoptosis were assessed. Results suggested that rAAV-PR39-ADM administration after myocardial infarction improved cell viability and cardiac function, attenuated apoptosis and myocardial injury, and promoted angiogenesis. Subsequently, levels of 6×His, HIF-1α, VEGF, p-Akt, Akt, ADM, Bcl-2, and Bax were measured by western blot. rAAV-PR39-ADM increased p-Akt, HIF-1α, and VEGF levels and induced higher Bcl-2 expression and lower Bax expression. In conclusion, our results demonstrate that rAAV-PR39-ADM mitigates myocardial injury by promoting angiogenesis and reducing apoptosis. This study suggests a potential novel gene therapy-based method that could be used clinically for myocardial infarction.
authors.affiliation: Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Rui
authors.initials: R
authors.lastname: An
authors.affiliation: Department of Neurology, Baoji City People's Hospital, Baoji, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Xi
authors.affiliation: Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an, China.
authors.forename: Shumiao
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuemin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuewen
authors.identifier: 0000-0002-8688-178X
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Lijun
authors.identifier: 0000-0002-0561-6934
authors.initials: L
authors.lastname: Sun
mesh_terms: D053607:Adrenomedullin / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; C072212:PR 39; D053607:Adrenomedullin; D051057:Proto-Oncogene Proteins c-akt