title: Overexpression of complement component C5a accelerates the development of atherosclerosis in ApoE-knockout mice.
abstract: BACKGROUND
  In this study, we investigated the direct effect of C5a overexpression on atherosclerosis.
  
  
  RESULTS
  A recombinant adenovirus expressing mouse C5a (Ad-C5a) was constructed and injected intravenously into ApoE-/- mice. After 12 weeks of a high-fat diet, Ad-C5a injection produced more extensive lesions than control adenovirus, and its proathrosclerotic role was significantly blocked by C5a receptor antagonist. Immunohistochemical analysis showed enhanced macrophage infiltration in atherosclerotic regions with C5a overexpression. Trans-well assay revealed C5a receptor-dependent chemotaxis of C5a to macrophages. Furthermore, Ad-C5a overexpression promoted foam cell formation and lipid deposition but reduced collagen content. In addition, with Ad-C5a overexpression, the serum levels of interleukin 6 and tumor necrosis factor α were upregulated.
  
  
  CONCLUSIONS
  C5a overexpression could accelerate the development of atherosclerosis in ApoE-/- mice by promoting macrophage recruitment, foam cell formation and inflammatory activation. Furthermore, its proatherogetic role is mediated by the C5a receptor.
authors: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors: Guipeng
authors: G
authors: An
authors: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors: Bo
authors: B
authors: Li
authors: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors: Xiaoman
authors: X
authors: Liu
authors: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors: Mingxiang
authors: M
authors: Zhang
authors: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors: Fei
authors: F
authors: Gao
authors: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors: Yuxia
authors: Y
authors: Zhao
authors: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors: Fengshuang
authors: F
authors: An
authors: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors: Yun
authors: Y
authors: Zhang
authors: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, China.|Department of Cardiology, Shandong University Qilu Hospital, Jinan, Shandong, China.
authors: Cheng
authors: C
authors: Zhang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology*; D002633:Chemotaxis; D015936:Complement C5a / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D005822:Genetic Vectors / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D010456:Peptides, Cyclic / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation
chemical_list: C438957:AcPhe(ornithine-Pro-cyclohexylamine-Trp-Arg); D015850:Interleukin-6; D010456:Peptides, Cyclic; D044087:Receptor, Anaphylatoxin C5a; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D015936:Complement C5a
keywords: C5a; Pathology Section; atherosclerosis; complement system