title: Impact of a combined high cholesterol diet and high glucose environment on vasculature.
abstract: OBJECTIVE
  Vascular complications are the leading cause of mortality and morbidity in patients with diabetes. However, proper animal models of diabetic vasculopathy that recapitulate the accelerated progression of vascular lesions in human are unavailable. In the present study, we developed a zebrafish model of diabetic vascular complications and the methodology for quantifying vascular lesion formation real-time in the living diabetic zebrafish.
  
  
  RESULTS
  Wild type zebrafish (AB) and transgenic zebrafish lines of fli1:EGFP, lyz:EGFP, gata1:dsRed, double transgenic zebrafish of gata1:dsRed/fli1:EGFP were exposed to high cholesterol diet and 3% glucose (HCD-HG) for 10 days. The zebrafish model with HCD-HG treatment was characterized by significantly increased tissue levels of insulin, glucagon, glucose, total triglyceride and cholesterol. Confocal microscopic analysis further revealed that the diabetic larvae developed clearly thickened endothelial layers, distinct perivascular lipid depositions, substantial accumulations of inflammatory cells in the injured vasculature, and a decreased velocity of blood flow. Moreover, the vascular abnormalities were improved by the treatment of pioglitazone and metformin.
  
  
  CONCLUSIONS
  A combination of high cholesterol diet and high glucose exposure induces a rapid onset of vascular complications in zebrafish similar to the early atherosclerotic vascular injuries in mammalian diabetic models, suggesting that zebrafish may be used as a novel animal model for diabetic vasculopathy.
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, P. R. China.
authors.forename: Zemin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, P. R. China ; Department of Cell Biology and Anatomy, South Carolina University, Columbus, South Carolina, United States of America.
authors.forename: Taixing
authors.initials: T
authors.lastname: Cui
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, P. R. China ; Center for Stem Cell and Regenerative Medicine, The Second Hospital of Shandong University, Jinan, P.R. China.
authors.forename: Dongqi
authors.initials: D
authors.lastname: Tang
authors.affiliation: Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, P. R. China.
authors.forename: Xing Li
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000009:adverse effects*; D003920:Diabetes Mellitus / Q000139:chemically induced* / Q000188:drug therapy*; D005947:Glucose / Q000009:adverse effects*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use; D015027:Zebrafish
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D008687:Metformin; D002784:Cholesterol; D005947:Glucose; D000077205:Pioglitazone