title: Increased plasma BMP-2 levels are associated with atherosclerosis burden and coronary calcification in type 2 diabetic patients.
abstract: BACKGROUND
  Although Bone morphogenetic protein-2 (BMP-2) is a known mediator of bone regeneration and vascular calcification, to date no study has investigated the relationship between BMP-2 and type 2 diabetes mellitus (T2DM) and its possible role in coronary artery disease (CAD). The purpose of this study is to evaluate the relationship of BMP-2 with atherosclerosis and calcification in patients with T2DM.
  
  
  METHODS
  124 subjects were enrolled in this study: 29 patients with T2DM and CAD; 26 patients with T2DM and without CAD; 36 patients with CAD and without T2DMand 34 without T2DM or CAD (control group). Severity of coronary lesions was assessed using coronary angiography and intravascular ultrasound (IVUS). Plasma BMP-2 levels were quantified using a commercially available ELISA kit.
  
  
  RESULTS
  Compared to the control group, the mean plasma BMP-2 level was significantly higher in T2DM patients with or without CAD (20.1 ± 1.7 or 19.3 ± 1.5 pg/ml, vs 17.2 ± 3.3 pg/ml, P < 0.001). In a multivariable linear regression analysis, both T2DM and CAD were significantly and positively associated with BMP-2 (Estimate, 0.249; standard error (SE), 0.063; p <0.0001; Estimate, 0.400; SE, 0.06; p < 0.0001). Plasma BMP-2 was also strongly correlated with glycosylated hemoglobin A1c (HbA1c) (Spearman ρ = -0.31; p = 0.0005). SYNTAX score was also significantly associated with BMP-2 (Spearman ρ = 0.46; p = 0.0002). Using the results from IVUS, plasma BMP-2 levels were shown to positively correlate with plaque burden (Spearman ρ = 0.38, P = 0.002) and plaque calcification (Spearman ρ =0.44, P = 0.0003) and to negatively correlate with lumen volume (Spearman ρ =0.31, P = 0.01).
  
  
  CONCLUSIONS
  Our study demonstrates that patients with T2DM had higher circulating levels of BMP-2 than normal controls. Plasma BMP-2 levels correlated positively with plaque burden and calcification in patients with T2DM.
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, PR China. zhangming2279@hotmail.com.|Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing, China. zhangming2279@hotmail.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Division of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN, USA. Sara.Jaskanwal@mayo.edu.
authors.forename: Jaskanwal Deep
authors.initials: JD
authors.lastname: Sara
authors.affiliation: Division of Cardiovascular Diseases, Mayo College of Medicine, Rochester, MN, USA. Wang.Fei-long@mayo.edu.
authors.forename: Fei-long
authors.initials: FL
authors.lastname: Wang
authors.affiliation: Department of Nephrology, First Hospital of Tsinghua University, Beijing, China. llp9076@icloud.com.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Liu
authors.affiliation: Department of Biostatistics, Rutgers School of Public Health, The State University of New Jersey, Piscataway, NJ, USA. sulixiaousa@gmail.com.
authors.forename: Li-Xiao
authors.initials: LX
authors.lastname: Su
authors.affiliation: Department of Biostatistics, University at Buffalo, the State University of New York, Buffalo, NY, 14214, USA. zhejing0@gmail.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhe
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, PR China. wuxi123@163.com.|Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing, China. wuxi123@163.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, PR China. liujinghua@vip.sina.com.
authors.forename: Jing-hua
authors.initials: JH
authors.lastname: Liu
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D055396:Bone Morphogenetic Protein 2 / Q000097:blood*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D018084:Ultrasonography, Interventional; D061205:Vascular Calcification / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2