title: GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Null Mice.
abstract: Growth differentiation factor 11 (GDF11) reduces cardiac hypertrophy, improves cerebral vasculature and enhances neurogenesis in ageing mice. Higher growth differentiation factor 11/8 (GDF11/8) is associated with lower risk of cardiovascular events in humans. Here, we showed that adeno-associated viruses-GDF11 and recombinant GDF11 protein improve endothelial dysfunction, decrease endothelial apoptosis, and reduce inflammation, consequently decrease atherosclerotic plaques area in apolipoprotein E-/-mice. Moreover, adeno-associated viruses-GDF11 and recombinant GDF11 stabilize atherosclerotic plaques by selectively decreasing in macrophages and T lymphocytes, while increasing in collagen and vascular smooth muscle cells within plaques. In addition, GDF11 inhibit palmitic acid-induced endothelial apoptosis and ameliorate palmitic acid-induced inflammatory response in RAW264.7 macrophages in vitro. Mechanistically, GDF11 activates the TGF-β/Smad2/3, AMPK/endothelial nitricoxide synthase (eNOS) while suppresses JNK and NF-κB pathways. In humans, circulating GDF11/8 is positively associated with flow-mediated endothelium-dependent dilation in overweight subjects. We concluded that adeno-associated viruses-GDF11 and recombinant GDF11 protect against endothelial injury and reduce atherosclerosis in apolipoprotein E-/-mice, thus may be providing a novel approach to the treatment of atherosclerosis.
authors: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, China.
authors: Wen
authors: W
authors: Mei
authors: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, China. Electronic address: Guangda64@hotmail.com.
authors: Guangda
authors: G
authors: Xiang
authors: Radiation-Diagnostic/Oncology School of Medicine, Emory University, Atlanta, Georgia, USA.
authors: Yixiang
authors: Y
authors: Li
authors: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, China.
authors: Huan
authors: H
authors: Li
authors: Mathematics and Statistics Department, Georgia State University, Atlanta, Georgia, USA.
authors: Lingwei
authors: L
authors: Xiang
authors: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, China.
authors: Junyan
authors: J
authors: Lu
authors: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, China.
authors: Lin
authors: L
authors: Xiang
authors: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, China.
authors: Jing
authors: J
authors: Dong
authors: Department of Endocrinology, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei Province, China.
authors: Min
authors: M
authors: Liu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000494:pharmacology; D055412:Growth Differentiation Factors / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019308:Palmitic Acid / Q000009:adverse effects; D000067996:RAW 264.7 Cells; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D019485:Bone Morphogenetic Proteins; C492266:GDF11 protein, human; D055412:Growth Differentiation Factors; D011994:Recombinant Proteins; D019308:Palmitic Acid