title: Pigment epithelium-derived factor is associated with necrotic core progression during statin therapy.
abstract: OBJECTIVE
  Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis and an important target molecule for preventing the progression of atherosclerosis. However, the relationship between PEDF and coronary atherosclerosis has not been fully examined. The aim of the present study is to evaluate the effects of statins on serum PEDF levels and the association between PEDF and coronary atherosclerosis.
  
  
  METHODS
  Coronary atherosclerosis in nonculprit lesions in the vessel of patients undergoing a percutaneous coronary intervention was evaluated using virtual histology intravascular ultrasound in 99 patients during percutaneous coronary intervention and after 8 months of statin therapy.
  
  
  RESULTS
  Serum PEDF levels at baseline and at the 8-month follow-up did not differ. A significant decrease in the fibro-fatty component (-0.24 mm³/mm, P=0.0003) and increases in the necrotic core (0.13 mm³/mm, P=0.02) and dense calcium components (0.11 mm³/mm, P<0.0001) were observed during the 8-month statin therapy. On univariate regression analyses, serum PEDF levels (r=0.291, P=0.004) and unstable angina pectoris (r=0.203, P=0.04) showed significant positive correlations with the percentage change in necrotic core volume. Multivariate regression analysis showed that serum PEDF level was a significant independent predictor associated with necrotic core progression during statin therapy (β=0.218, P=0.04).
  
  
  CONCLUSIONS
  Statin therapy had no effects on serum PEDF levels. Serum PEDF was a useful biomarker for predicting necrotic core progression during statin therapy, and its levels could be elevated as a counter-regulatory response mechanism to protect against necrotic core progression.
authors.affiliation: aDivision of Cardiology, Department of Internal Medicine, Yokohama Sakae Kyosai Hospital bDepartment of Cardiology, Tsurumi Nishiguchi Hospital cDepartment of Cardiology, Yokohama Seamen's Insurance Hospital dDepartment of Cardiology, Kanagawa Cardiovascular and Respiratory Center eDivision of Cardiology, Yokohama City University Medical Center, Yokohama fDepartment of Pathophysiology and Therapeutic of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume gFirst Department of Internal Medicine, Showa University School of Medicine, Tokyo hDepartment of Cardiology, Hiratsuka Kyosai Hospital, Hiratsuka iFourth Department of Internal Medicine, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki jCardiovascular Imaging Center, Toyohashi, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nozue
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hirano
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tohyama
authors.forename: Kazuki
authors.initials: K
authors.lastname: Fukui
authors.forename: Shigeo
authors.initials: S
authors.lastname: Umezawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Onishi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kunishima
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hibi
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Terashima
authors.forename: Ichiro
authors.initials: I
authors.lastname: Michishita
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000188:drug therapy; D011480:Protease Inhibitors / Q000097:blood*; D015843:Serpins / Q000097:blood*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D015415:Biomarkers; D002784:Cholesterol; D005136:Eye Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009414:Nerve Growth Factors; D011480:Protease Inhibitors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor