title: Systemic activation of integrin alphaVbeta3 in donors with spontaneous intracerebral hemorrhage is associated with subsequent development of vasculopathy in the heart transplant recipient.
abstract: BACKGROUND
  Recipients of hearts from donors with spontaneous intracerebral hemorrhage (ICH) are at increased risk of allograft vasculopathy compared with trauma donors. We have recently shown that the vitronectin receptor (integrin alpha(V)beta3) is upregulated in transplant vasculopathy. We hypothesized that donor ICH is associated with systemic activation of alpha(V)beta3 in the donor before transplantation.
  
  
  METHODS
  We evaluated mRNA expressions of alpha(V)beta3 (TaqMan PCR) in endomyocardial biopsy samples at 1-week post-transplant in 20 recipients from ICH donors and 20 recipients from trauma donors. To investigate whether systemic activation of alpha(V)beta3 was present in the donor before transplantation, alpha(V)beta3 expression was also evaluated in the corresponding donor spleen lymphocytes. All patients underwent serial coronary intravascular ultrasound to evaluate for coronary vasculopathy. The baseline characteristics were similar except for increased donor age in the ICH Group.
  
  
  RESULTS
  The ICH Group showed significant increased mRNA expression of alpha(V)beta3 in the heart biopsy samples (3.8-fold, p = 0.012) and in the corresponding donor spleen lymphocytes (3.5-fold, p = 0.014) compared with the Trauma Group. At 1 year, the ICH Group also showed increased progression of coronary vasculopathy. Multivariate regression analysis found that donor lymphocytic alpha(V)beta3 mRNA expression was independently associated with increased risk of vasculopathy (odds ratio, 1.9; 95% CI, 1.21-3.98, p = 0.03).
  
  
  CONCLUSIONS
  Our report demonstrates the presence of systemic activation of alpha(V)beta3 in donors with spontaneous intracerebral hemorrhage and its association with the subsequent development of allograft vasculopathy in the recipient.
authors.affiliation: Department of Cardiovascular Medicine, Kaufman Center for Heart Failure, The Cleveland Clinic Foundation, Ohio, USA. Yamanim@ccf.org
authors.forename: Mohamad H
authors.initials: MH
authors.lastname: Yamani
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cook
authors.forename: E Murat
authors.initials: EM
authors.lastname: Tuzcu
authors.forename: Philip
authors.initials: P
authors.lastname: Paul
authors.forename: Norman B
authors.initials: NB
authors.lastname: Ratliff
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Robert
authors.initials: R
authors.lastname: Hobbs
authors.forename: Gustavo
authors.initials: G
authors.lastname: Rincon
authors.forename: Corinne
authors.initials: C
authors.lastname: Bott-Silverman
authors.forename: Nicholas
authors.initials: N
authors.lastname: Smedira
authors.forename: James B
authors.initials: JB
authors.lastname: Young
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
mesh_terms: D001483:Base Sequence; D001707:Biopsy, Needle; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000175:diagnosis; D004699:Endocardium / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival; D016027:Heart Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D011300:Preoperative Care; D015995:Prevalence; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D014019:Tissue Donors; D014184:Transplantation, Homologous; D018084:Ultrasonography, Interventional; D014652:Vascular Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000209:etiology*
chemical_list: D039302:Integrin alphaVbeta3; D012333:RNA, Messenger