title: Myocardial proinflammatory cytokine expression and left ventricular remodeling in patients with chronic mitral regurgitation.
abstract: BACKGROUND
  In an animal model, stretch was shown to induce myocardial tumor necrosis factor-alpha (TNF-alpha) expression. The purposes of this study were to determine whether the left ventricular (LV) volume overload that occurs in patients with chronic mitral regurgitation (MR) can induce myocardial and systemic TNF-alpha expression and whether there is a relationship between TNF-alpha expression and LV remodeling.
  
  
  RESULTS
  Plasma TNF-alpha and its receptors were measured before mitral valve (MV) repair surgery in 26 MR patients and 23+/-12 months after MV repair surgery in 9 MR patients. Myocardial mRNA copies of TNF-alpha were determined in 11 MR and 10 donor hearts using quantitative RT-PCR. Compared with 15 control subjects, pre-MV repair plasma TNF-alpha (3.59+/-1.81 versus 2.03+/-1.02 pg/mL, P<0.005) and its receptor levels were elevated in MR patients. Myocardial TNF-alpha mRNA copies (corrected for beta-actin mRNA expression) in MR patients and donor hearts were 38.96+/-42.74x10(6) and 0.88+/-0.75x10(6), respectively (P=0.01). After MV surgery, there was a decrease in the plasma levels of TNF-alpha (2.79+/-1.14 versus 3.51+/-1.34 pg/mL, P=0.02) and its receptors. There was a correlation between myocardial TNF-alpha expression and preoperative LV end-diastolic and end-systolic volumes. Moreover, there was an inverse correlation between myocardial TNF-alpha expression and regression in LV end-diastolic (r=-0.76, P=0.007) and end-systolic (r=-0.73, P=0.01) volumes after MV surgery.
  
  
  CONCLUSIONS
  TNF-alpha is expressed in the myocardium and plasma of MR patients. Correction of the LV volume overload with MV surgery results in reversal of TNF-alpha expression. There is a relationship between TNF-alpha expression and parameters of LV remodeling, suggesting that TNF-alpha may play a role in the pathogenesis of the LV remodeling that occurs in MR.
authors.affiliation: Division of Cardiology, University of Michigan and Veterans Affairs Medical Centers, Ann Arbor, USA. oralh@umich.edu
authors.forename: Hakan
authors.initials: H
authors.lastname: Oral
authors.forename: Natarajan
authors.initials: N
authors.lastname: Sivasubramanian
authors.forename: David B
authors.initials: DB
authors.lastname: Dyke
authors.forename: Rajendra H
authors.initials: RH
authors.lastname: Mehta
authors.forename: P Michael
authors.initials: PM
authors.lastname: Grossman
authors.forename: Kerri
authors.initials: K
authors.lastname: Briesmiester
authors.forename: William P
authors.initials: WP
authors.lastname: Fay
authors.forename: Francis D
authors.initials: FD
authors.lastname: Pagani
authors.forename: Steven F
authors.initials: SF
authors.lastname: Bolling
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
authors.forename: Mark R
authors.initials: MR
authors.lastname: Starling
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D001706:Biopsy; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000601:surgery; D008944:Mitral Valve Insufficiency / Q000503:physiopathology* / Q000601:surgery; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D011184:Postoperative Period; D012333:RNA, Messenger / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012016:Reference Values; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020257:Ventricular Remodeling
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha