title: Diabetes modifies the relationships among carotid plaque calcification, composition and inflammation.
abstract: OBJECTIVE
  Diabetes is traditionally associated with vascular calcification, but the molecular mechanisms are largely unknown. We herein explored the relationships among carotid plaque calcification, composition and gene expression, and how these are modified by diabetes.
  
  
  METHODS
  We collected carotid endoarterectomy specimen from 59 patients, of whom 23 had diabetes. We analysed histology with pentachromic staining, calcification with Alizarin red and Von Kossa's staining, chemical calcium extraction and quantification, as well as gene expression by quantitative PCR.
  
  
  RESULTS
  We detected no differences in the extent of plaque calcification and in plaque composition between diabetic and non-diabetic patients. In non-diabetic plaques, calcium content was directly correlated with the area occupied by muscle/fibrinoid tissue and inversely correlated with collagen, but such correlations were not seen in plaques from diabetic patients. While consistent correlations were found between calcium content and RUNX2 (direct), as well as Osteopontin (inverse), diabetes modified the association between plaque calcification and inflammatory gene expression. Only in diabetic plaques, calcium content was inversely correlated with MCP1 and IL1b, whereas the direct correlation with TNF-alpha expression seen in non-diabetic plaques was lost in diabetes.
  
  
  CONCLUSIONS
  Though plaque composition and calcification were not quantitatively affected, diabetes modified the relationships between plaque calcium, composition and inflammation. These results suggest that the mechanisms and the clinical significance of atherosclerotic calcification in diabetic may be different than in non-diabetic patients.
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Menegazzo
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Nicol
authors.initials: N
authors.lastname: Poncina
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Albiero
authors.affiliation: Department of Cardiac, Vascular and Thoracic Sciences, University of Padova, Padova, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Menegolo
authors.affiliation: Department of Cardiac, Vascular and Thoracic Sciences, University of Padova, Padova, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Grego
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.affiliation: Department of Medicine, University of Padova, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy. Electronic address: gianpaolo.fadini@unipd.it.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D016893:Carotid Stenosis / Q000150:complications / Q000473:pathology*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D048909:Diabetes Complications / Q000175:diagnosis / Q000473:pathology*; D016894:Endarterectomy, Carotid; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000473:pathology*; D061205:Vascular Calcification / Q000150:complications / Q000473:pathology*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D050659:Core Binding Factor Alpha 1 Subunit; C508585:IL1B protein, human; D053583:Interleukin-1beta; C493709:RUNX2 protein, human; C506895:SPP1 protein, human; D053495:Osteopontin
keywords: Atherosclerosis; Calcification; Diabetes; Inflammation; Stability