title: Differential expression of the angiotensin-(1-12)/chymase axis in human atrial tissue.
abstract: OBJECTIVE
  Heart chymase rather than angiotensin converting enzyme has higher specificity for angiotensin (Ang) I conversion into Ang II in humans. A new pathway for direct cardiac Ang II generation has been revealed through the demonstration that Ang-(1-12) is cleaved by chymase to generate Ang II directly. We address here whether Ang-(1-12) and chymase gene expression and activity are detected in the atrial appendages of 44 patients (10 females) undergoing heart surgery for the correction of valvular heart disease, resistant atrial fibrillation or ischemic heart disease.
  
  
  RESULTS
  Immunoreactive Ang-(1-12) expression was 54% higher in left atrial compared with right atrial appendages. This was associated with higher abundance of left atrial appendage chymase gene transcripts and chymase activity, but no differences in angiotensinogen mRNA. Atrial chymase enzymatic activity was highly correlated with left atrial but not right atrial enlargement as determined by echocardiography, while both tyrosine hydroxylase and neuropeptide Y atrial appendage mRNAs correlated with atrial angiotensinogen mRNAs.
  
  
  CONCLUSIONS
  Higher Ang-(1-12) expression and upregulation of chymase gene transcripts and enzymatic activity from the atrial appendages connected to the enlarged left versus right atrial chambers of subjects with left heart disease defines a role of this alternate Ang II forming pathway in the processes accompanying adverse atrial and ventricular remodeling.
authors.affiliation: Division of Surgical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Nagata
authors.affiliation: Division of Surgical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, NC, USA Department of Physiology/Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Varagic
authors.affiliation: Cardiothoracic Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Kon
authors.affiliation: Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, NC, USA Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, NC, USA Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Leanne
authors.initials: L
authors.lastname: Groban
authors.affiliation: Division of Surgical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Simington
authors.affiliation: Division of Surgical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Sarfaraz
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Birmingham Veterans Affair Medical Center, University of Alabama Medical Center, Birmingham, AL, USA Division of Cardiovascular Disease, Department of Medicine, University of Alabama Medical Center, Birmingham, AL, USA.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Dell'Italia
authors.affiliation: Division of Surgical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: VonCannon
authors.affiliation: Cardiothoracic Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Dwight
authors.initials: D
authors.lastname: Deal
authors.affiliation: Division of Surgical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA cferrari@wakehealth.edu.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Ferrario
mesh_terms: D000368:Aged; D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000808:Angiotensinogen / Q000235:genetics; D001281:Atrial Fibrillation / Q000601:surgery; D053818:Chymases / Q000235:genetics*; D004452:Echocardiography; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006325:Heart Atria / Q000201:enzymology*; D006349:Heart Valve Diseases / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D020257:Ventricular Remodeling
chemical_list: D012333:RNA, Messenger; D000808:Angiotensinogen; D000804:Angiotensin II; D000803:Angiotensin I; D053818:Chymases
keywords: angiotensin II; angiotensin converting enzyme inhibitors; antihypertensive therapy; aortic valve disease; arrhythmia; cardiac chymase; coronary heart disease; enzymes; heart surgery