VEGF nanoparticles repair the heart after myocardial infarction

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 314; no. 2; pp. H278 - H284
• Main Authors: Oduk, Yasin, Zhu, Wuqiang, Kannappan, Ramaswamy, Zhao, Meng, Borovjagin, Anton V., Oparil, Suzanne, Zhang, Jianyi (Jay)
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.02.2018
• Series: Integrative Cardiovascular Physiology and Pathophysiology
• Subjects: Acids; Angiogenesis; Angiogenesis Inducing Agents - administration & dosage; Angiogenesis Inducing Agents - chemistry; Animals; Cells, Cultured; Coronary artery disease; Cytokines; Delayed-Action Preparations; Disease Models, Animal; Drug Carriers; Drug Compounding; Encapsulation; Heart; Heart attacks; Heart diseases; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Ischemia; Medical treatment; Mice, Inbred NOD; Mice, SCID; Muscle contraction; Myocardial Contraction - drug effects; Myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Nanoparticles; Neovascularization, Physiologic - drug effects; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Recovery of Function; Time Factors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - administration & dosage; Vascular Endothelial Growth Factor A - chemistry; Vascularization; Ventricle; Ventricular Function, Left - drug effects; Ventricular Remodeling - drug effects; nanoparticle; revascularization; sustained release; vascular endothelial growth factor; cardiac tissue; myocardial infarction
• ISSN: 0363-6135; 1522-1539; 1522-1539
• DOI: 10.1152/ajpheart.00471.2017

Vascular endothelial growth factor (VEGF) is a well-characterized proangiogenic cytokine that has been shown to promote neovascularization in hearts of patients with ischemic heart disease but can also lead to adverse effects depending on the dose and mode of delivery. We investigated whether prolonged exposure to a low dose of VEGF could be achieved by encapsulating VEGF in polylactic coglycolic acid nanoparticles and whether treatment with VEGF-containing nanoparticles improved cardiac function and protected against left ventricular remodeling in the hearts of mice with experimentally induced myocardial infarction. Polylactic coglycolic acid nanoparticles with a mean diameter of ~113 nm were generated via double emulsion and loaded with VEGF; the encapsulation efficiency was 53.5 ± 1.7% (107.1 ± 3.3 ng VEGF/mg nanoparticles). In culture, VEGF nanoparticles released VEGF continuously for at least 31 days, and in a murine myocardial infarction model, VEGF nanoparticle administration was associated with significantly greater vascular density in the peri-infarct region, reductions in infarct size, and improvements in left ventricular contractile function 4 wk after treatment. Thus, our study provides proof of principle that nanoparticle-mediated delivery increases the angiogenic and therapeutic potency of VEGF for the treatment of ischemic heart disease. NEW & NOTEWORTHY Vascular endothelial growth factor (VEGF) is a well-characterized proangiogenic cytokine but has a short half-life and a rapid clearance rate. When encapsulated in nanoparticles, VEGF was released for 31 days and improved left ventricular function in infarcted mouse hearts. These observations indicate that our new platform increases the therapeutic potency of VEGF.