title: Systemic up-regulation of angiotensin II type 1 receptor in cardiac donors with spontaneous intracerebral hemorrhage.
abstract: Donor spontaneous intracerebral hemorrhage (ICH) is a potential risk factor for morbidity and mortality after cardiac transplantation. We hypothesized that donor ICH is associated with systemic up-regulation of angiotensin II receptor type 1 (AT1R). We evaluated mRNA expression of AT1R and AT2R in donor spleen lymphocytes and in heart biopsies from 20 recipients of hearts from donors with spontaneous ICH which were compared with 20 recipients from trauma donors. Heart biopsies showed 4.7-fold increased mRNA expression of AT1R (p < 0.0001) in the ICH group compared with the Trauma group. The ICH group also showed 2.6-fold (p < 0.01) increased mRNA expression of AT1R in the donor spleen lymphocytes, suggesting the presence of systemic activation before transplantation. At 1 year, the ICH group had increased coronary vasculopathy by vascular ultrasound. Using multivariate regression analysis, mRNA expression of AT1R in the donor spleen lymphocytes was found to be a strong independent predictor of transplant vasculopathy (odds ratio = 4.397, CI = 1.243-15.553, adjusted p = 0.02). This is the first report to describe splenic up-regulation of AT1R in the presence of spontaneous ICH and its association with subsequent development of transplant vasculopathy.
authors.affiliation: Department of Cardiovascular Medicine, Kaufman Center for Heart Failure, The Cleveland Clinic Foundation, Cleveland, OH, 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: Ashraf
authors.initials: A
authors.lastname: Abdo
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: Mohammad
authors.initials: M
authors.lastname: Yousufuddin
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
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: Patrick M
authors.initials: PM
authors.lastname: McCarthy
authors.forename: James B
authors.initials: JB
authors.lastname: Young
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
mesh_terms: D000328:Adult; D001706:Biopsy; D017690:Cell Transplantation; D002543:Cerebral Hemorrhage / Q000209:etiology*; D017931:DNA Primers / Q000737:chemistry; D004699:Endocardium / Q000473:pathology; D005260:Female; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis*; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012313:RNA