Targeted transfection of Ang-1 gene via microbubbles carrying ICAM-1 antibody to acute myocardial infarction
10.3760/cma.j.issn.1004-4477.2011.05.022
- VernacularTitle:携抗ICAM-1靶向微泡定向转染Ang-1基因治疗急性心肌梗死的实验研究
- Author:
Xiao WANG
;
Ruiqiang GUO
;
Qing ZHOU
;
Qian CHEN
;
Jinling CHEN
- Publication Type:Journal Article
- Keywords:
Microbubbles;
Transfection;
Myocardial infarction;
Intercellual adhesion molecule-1;
Angiopoietin-1
- From:
Chinese Journal of Ultrasonography
2011;20(5):436-440
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the capability of Ang-1 gene delivery to acute myocardial infarction using targeted microbubbles carrying ICAM-1 antibody.Methods Thirty-seven rabbits' left circumfles branch coronary arteries were ligated for models.Three rabbits were injected with microbubbles carrying ICAM-1 to detect the ability of targeting.Thirty-four rabbit models were divided into 3 groups randomly as follow:IM group (n=12,accept direct intramuscular injection),ICAM-1 group (n=12,accept intravenous injection of targeted microbubbles and Ang-1) and control group (n=10,without any treatment).Ultrasonography were executed on all animals before and 2 weeks after the treatment.All rabbits were killed after 2 weeks and examined for Ang-1 mRNA and protein by RT-PCR and Western-Blot respectively.Microvessel density (MVD) counting of infracted myocardium,observed by factor Ⅷ immunochemical staining,was performed to value the proangiogenesis effect of Ang-1 delivered by targeted microbubbles carrying ICAM-1 antibody.The liver and the kidney in ICAM-1 group were taken to assess the systemic delivery.Results IM and ICAM-1 group showed significantly improvement in the ejection fraction (P<0.05) while control group did not.Ang-1 mRNA and protein could be detected in IM and ICAM-1 group;however,the expression between the two groups showed no siginificant difference.None of the control animals showed Ang-1 expression.compared with ICAM-1 group,the MVD was greater in IM group.Ang-1 was not detected either in liver or in kidney in ICAM-1 group.Conclusions Targeted microbubbles carrying ICAM-1 antibody can deliver Ang-1 gene to ischemic myocardium directly.Meanwhile,it's as effective as IM injections besides the greater angiogenesis effect.This strategy improves the perfusion of acute myocardial infarction and the function of heart.