title: Nestin and WT1 expression in atheromathous plaque neovessels: association with vulnerability.
abstract: Neoangiogenesis is crucial for the progression and vulnerability of atheromasic lesions. Since adult vasa vasorum, which represent the neoangiogenetic burden of healthy arteries, constitutively express Nestin and Wilms Tumor (WT1), the aims of the present study are: i) to describe and quantify Nestin and WT1 in plaque neovessels; ii) to investigate the relationship between neovessel phenotype and plaque instability.
  
  
  
  We prospectively evaluated 49 consecutive carotid endarterectomy specimens. Histopathological characteristics were separately collected, particularly the intraplaque histological complications. Immunohistochemistry was carried out for CD34, Nestin and WT1; the density of positivity was evaluated for each marker. RT-PCR was performed to assess Nestin and WT1 mRNA levels on the first 10 plaques and on 10 control arteries.
  
  
  
  Six (12.2%) plaques showed no neoangiogenesis. In the others, the mean immunohistochemical densities of CD34, Nestin, and WT1-positive structures were 41.88, 28.84 and 17.68/mm2. Among the CD34+ neovessels, 68% and 42% expressed Nestin and WT1 respectively, i.e., nearly 36% of the neovessels resulted to be Nestin+/WT1-. Furthermore, complicated plaques (n=30) showed significantly more CD34 and Nestin-positive vessels than uncomplicated plaques (n=13; P=0.045 and P=0.009), while WT1 was not increased (P=0.139). RT-PCR confirmed that WT1 gene expression was 3-fold lower than Nestin gene in plaques (p=0.001).
  
  
  
  Plaque neoangiogenesis shows both a Nestin+/WT1- and a Nestin+/WT1+ phenotype. The Nestin+/WT1- neovessels are significantly more abundant in complicated (vulnerable) plaques. The identification of new transcription factors in plaque neoangiogenesis, and their possible regulation, can open new perspectives in the therapy of vulnerable plaques.
authors.affiliation: Unit of Vascular Surgery, Department of Specialty, Diagnostic and Experimental Medicine (DIMES), S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fittipaldi
authors.affiliation: Unit of Vascular Surgery, and Unit of Surgical Pathology, Department of Specialty, Diagnostic and Experimental Medicine (DIMES), S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Vasuri
authors.affiliation: Unit of Surgical Pathology, Department of Specialty, Diagnostic and Experimental Medicine (DIMES), S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Degiovanni
authors.affiliation: Unit of Vascular Surgery, Department of Specialty, Diagnostic and Experimental Medicine (DIMES), S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Pini
authors.affiliation: Unit of Vascular Surgery, Department of Specialty, Diagnostic and Experimental Medicine (DIMES), S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mauro
authors.affiliation: Unit of Vascular Surgery, Department of Specialty, Diagnostic and Experimental Medicine (DIMES), S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Faggioli
authors.affiliation: Unit of Surgical Pathology, Department of Specialty, Diagnostic and Experimental Medicine (DIMES), S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: D'Errico-Grigioni
authors.affiliation: Unit of Vascular Surgery, Department of Specialty, Diagnostic and Experimental Medicine (DIMES), S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Stella
authors.affiliation: Unit of Surgical Pathology, Department of Specialty, Diagnostic and Experimental Medicine (DIMES), S.Orsola-Malpighi Hospital, Bologna University, Bologna, Italy. gianandr.pasquinelli@unibo.it.
authors.forename: Gianandrea
authors.initials: G
authors.lastname: Pasquinelli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000473:pathology*; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D064231:Nestin / Q000032:analysis / Q000096:biosynthesis*; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025721:WT1 Proteins / Q000032:analysis / Q000096:biosynthesis*
chemical_list: C577484:NES protein, human; D064231:Nestin; D025721:WT1 Proteins; C583751:WT1 protein, human