title: Increased vascularization of shoulder regions of carotid atherosclerotic plaques from patients with diabetes.
abstract: OBJECTIVE
  Increased vascularization is considered an important contributing factor for plaque vulnerability. Microvascular proliferative disease in patients with diabetes results in renal damage and visual loss. We assessed the hypothesis that vascularization in carotid atherosclerotic tissue is increased in diabetic patients, especially in the critical shoulder regions of the plaque.
  
  
  METHODS
  Carotid endarterectomy specimens, clinical data, and blood samples were collected from patients with symptomatic carotid artery stenosis (median 85 days after clinical event) and pharmacologic treatment for diabetes (n = 26) or no diabetes (n = 85). Plaques were fixed in formalin and transverse tissue sections prepared. Histopathology and immunohistochemistry were performed for detection of endothelial cells (anti-CD34), macrophages (anti-CD68), vascular endothelial growth factor (VEGF), and its receptor (VEGFR-2). Neovascularization was assessed as CD34(+) neovessel density in the entire section area and by the presence or absence of CD34(+) vessels in the shoulder and cap regions of the plaques.
  
  
  RESULTS
  The patient groups did not differ significantly in neovascularization in the entire transverse sections (2.0 vs 2.1 vessels/mm(2); P = .61) or in the fibrous cap (52% of the patients in both groups; P = .95). Neovascularization of the plaque shoulder regions was observed in 52% of the diabetic patients and in 26% of the nondiabetic patients (P = .028). VEGF-stained areas were similar in the two patient groups (0.4% and 0.2% of shoulder area; P = .61). Patients with diabetes had more VEGFR-2 (1.0% vs 0.2% of shoulder area; P < .016) and less CD68 staining (0.4% vs 3.6% of shoulder area; P < .008). Time from clinical event to surgery was positively associated with neovascularization of the plaque shoulder regions (≤90 days, 18% of patients; >90 days, 50% of patients; P = .002), independently of diabetes status.
  
  
  CONCLUSIONS
  Diabetes was associated with increased vascularization of the shoulder regions in patients with symptomatic carotid atherosclerotic plaques. This was accompanied by increased expression of VEGFR-2. The increased vascularization of the plaque shoulder regions may help explain why patients with diabetes are at increased risk of atherosclerotic complications.
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research, Institute of Medicine, the Sahlgrenska Academy at the University of Gothenburg and Wallenberg Laboratory, Gothenburg, Sweden.
authors.forename: Fredrik J
authors.initials: FJ
authors.lastname: Olson
authors.forename: Sofia
authors.initials: S
authors.lastname: Strömberg
authors.forename: Ola
authors.initials: O
authors.lastname: Hjelmgren
authors.forename: Josefin
authors.initials: J
authors.lastname: Kjelldahl
authors.forename: Björn
authors.initials: B
authors.lastname: Fagerberg
authors.forename: Göran M L
authors.initials: GM
authors.lastname: Bergström
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016894:Endarterectomy, Carotid; D042783:Endothelial Cells / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008264:Macrophages / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D058226:Plaque, Atherosclerotic / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C467484:VEGFA protein, human