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Pre‐emptive heme oxygenase‐1 (HO‐1) gene delivery reduces mortality and preserves left ventricular function one‐year after acute myocardial infarction
Author(s) -
Liu Xiaoli,
Simpson Jeremy,
Brunt Keith,
Hall Sean,
Kinobe Robert,
Ogunyankin Kofo,
Ward Christopher
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1224-d
Subject(s) - medicine , myocardial infarction , cardiology , gene delivery , ventricular remodeling , heart failure , ischemia , heme oxygenase , cardiac function curve , artery , infarction , ligation , genetic enhancement , heme , gene , biology , biochemistry , enzyme
We reported previously that pre‐delivery of HO‐1 gene to the heart by adeno‐associated virus (AAV) markedly reduces ischemia and reperfusion (I/R) injury. However, the effect of pre‐emptive HO‐1 gene delivery on long‐term survival and LV structure and function has not been determined. We assessed the effect of HO‐1 gene delivery on long term survival, myocardial function and LV remodeling 1 year after myocardial infarction (MI) using echocardiography, pressure‐volume (PV) analysis and morphometric approaches. Two groups of Lewis rats were injected with 2 x 10 11 particles of AAV‐LacZ or AAV‐hHO‐1 in the apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and analysis of LV function were obtained at 12 months after MI. One year after MI, mortality was markedly reduced in the HO‐1 animals. PV analysis showed enhanced LV developed pressure, elevated maximal dP/dt and lower end diastolic volume in the HO‐1 compared to the LacZ animals. Echocardiography showed a larger apical anterior‐to‐posterior wall ratio in HO‐1 animals. Morphometric analysis revealed a 62% decrease in myocardial scarring and fibrosis in the HO‐1 relative to the LacZ animals. We conclude that pre‐emptive HO‐1 gene delivery may be useful as a therapeutic strategy to reduce post MI LV remodeling and heart failure. Supported by CIHR grants to L.G. Melo and C.A. Ward