title: Sustained Placental Growth Factor-2 Treatment Does Not Aggravate Advanced Atherosclerosis in Ischemic Cardiomyopathy.
abstract: Angiogenic growth factor therapy for ischemic cardiovascular disease carries a risk of stimulating atherosclerotic plaque growth. We evaluated risk benefit ratio of sustained administration of recombinant human placental growth factor (rhPlGF)-2 in mice with advanced atherosclerosis and chronic ischemic cardiomyopathy. We maintained apolipoprotein E-deficient mice on a high cholesterol diet and induced myocardial infarction by transient ligation at 4 weeks. At 8 weeks, we assessed left ventricular (LV) function and randomized mice to receive rhPlGF-2 or vehicle (VEH) subcutaneously for 28 days. Administration of rhPlGF-2 significantly increased PlGF plasma levels without adverse hemodynamic or systemic inflammatory effects. RhPlGF-2 did not increase plaque area, composition, or vulnerability in the aortic arch. RhPlGF-2 significantly improved contractile function and reduced LV end-systolic and end-diastolic volume indices with a concomitant increase in capillary and arteriolar density in ischemic myocardium. RhPlGF-2 may represent a promising therapeutic strategy in chronic ischemic cardiomyopathy.
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.|CoBioRes, NV, Leuven, Belgium.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0003-2810-9000
authors.initials: P
authors.lastname: Pokreisz
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
authors.forename: Melissa
authors.initials: M
authors.lastname: Swinnen
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Caluwe
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
authors.forename: Hilde
authors.initials: H
authors.lastname: Gillijns
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
authors.forename: Nina
authors.initials: N
authors.lastname: Vanden Driessche
authors.affiliation: CoBioRes, NV, Leuven, Belgium.
authors.forename: Andrea
authors.initials: A
authors.lastname: Casazza
authors.affiliation: Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.|CoBioRes, NV, Leuven, Belgium.
authors.forename: Desire
authors.initials: D
authors.lastname: Collen
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000, Leuven, Belgium. stefan.janssens@kuleuven.be.
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001018:Aortic Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D002791:Cholesterol, Dietary; D002908:Chronic Disease; D004195:Disease Models, Animal; D055104:Infusions, Subcutaneous; D008297:Male; D000074085:Mice, Knockout, ApoE; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D000072483:Placenta Growth Factor / Q000008:administration & dosage* / Q000633:toxicity; D058226:Plaque, Atherosclerotic; D011994:Recombinant Proteins / Q000008:administration & dosage; D020127:Recovery of Function; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D059289:Vascular Stiffness / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D002791:Cholesterol, Dietary; C000608036:PGF protein, human; D011994:Recombinant Proteins; D000072483:Placenta Growth Factor
keywords: Angiogenesis; Atherosclerosis; Growth factor; Ischemic cardiomyopathy; Placental growth factor-2