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.
Keywords:
Angiogenesis; Atherosclerosis; Growth factor; Ischemic cardiomyopathy; Placental growth factor-2.
MeSH terms
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Angiogenesis Inducing Agents / administration & dosage*
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Angiogenesis Inducing Agents / toxicity
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Animals
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Aorta / drug effects*
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Aorta / pathology
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Aorta / physiopathology
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Aortic Diseases / drug therapy*
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Aortic Diseases / pathology
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Aortic Diseases / physiopathology
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Atherosclerosis / drug therapy*
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Atherosclerosis / pathology
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Atherosclerosis / physiopathology
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Cardiomyopathies / diagnostic imaging
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Cardiomyopathies / drug therapy*
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Cardiomyopathies / physiopathology
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Cholesterol, Dietary
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Chronic Disease
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Disease Models, Animal
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Infusions, Subcutaneous
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Male
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Mice, Knockout, ApoE
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Myocardial Contraction / drug effects
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Myocardial Infarction / diagnostic imaging
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Myocardial Infarction / drug therapy*
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Myocardial Infarction / physiopathology
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Neovascularization, Physiologic / drug effects*
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Placenta Growth Factor / administration & dosage*
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Placenta Growth Factor / toxicity
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Plaque, Atherosclerotic
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Recombinant Proteins / administration & dosage
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Recovery of Function
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Stroke Volume / drug effects
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Time Factors
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Vascular Stiffness / drug effects
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Ventricular Function, Left / drug effects*
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Ventricular Remodeling / drug effects
Substances
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Angiogenesis Inducing Agents
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Cholesterol, Dietary
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PGF protein, human
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Recombinant Proteins
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Placenta Growth Factor