title: Beneficial effects of selective HDL-raising gene transfer on survival, cardiac remodelling and cardiac function after myocardial infarction in mice.
abstract: Post-myocardial infarction (MI) ejection fraction is decreased in patients with low high-density lipoprotein (HDL) cholesterol levels, independent of the degree of coronary atherosclerosis. The objective of this study is to evaluate whether selective HDL-raising gene transfer exerts cardioprotective effects post MI. Gene transfer in C57BL/6 low-density lipoprotein receptor (LDLr)(-/-) mice was performed with the E1E3E4-deleted adenoviral vector AdA-I, inducing hepatocyte-specific expression of human apo A-I, or with the control vector Adnull. A ligation of the left anterior descending coronary artery was performed 2 weeks after transfer or saline injection. HDL cholesterol levels were persistently 1.5-times (P<0.0001) higher in AdA-I mice compared with controls. Survival was increased (P<0.01) in AdA-I MI mice compared with control MI mice during the 28-day follow-up period (hazard ratio for mortality 0.42; 95% confidence interval 0.24-0.76). Longitudinal morphometric analysis demonstrated attenuated infarct expansion and inhibition of left ventricular (LV) dilatation in AdA-I MI mice compared with controls. AdA-I transfer exerted immunomodulatory effects and increased neovascularisation in the infarct zone. Increased HDL after AdA-I transfer significantly improved systolic and diastolic cardiac function post MI, and led to a preservation of peripheral blood pressure. In conclusion, selective HDL-raising gene transfer may impede the development of heart failure.
authors.affiliation: Centre for Molecular and Vascular Biology, Department of Cardiovascular Sciences, Catholic University of Leuven, Leuven, Belgium.
authors.forename: S C
authors.initials: SC
authors.lastname: Gordts
authors.forename: I
authors.initials: I
authors.lastname: Muthuramu
authors.forename: E
authors.initials: E
authors.lastname: Nefyodova
authors.forename: F
authors.initials: F
authors.lastname: Jacobs
authors.forename: E
authors.initials: E
authors.lastname: Van Craeyveld
authors.forename: B
authors.initials: B
authors.lastname: De Geest
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000503:physiopathology / Q000517:prevention & control*; D006334:Heart Function Tests; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D013534:Survival; D019076:Transgenes; D020257:Ventricular Remodeling
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D011973:Receptors, LDL