title: C-reactive protein co-expresses with tumor necrosis factor-alpha in the myocardium in human dilated cardiomyopathy.
abstract: BACKGROUND
  C-reactive protein (CRP) has recently been reported to be present in cardiac tissue and to stimulate the production of proinflammatory cytokines. Cardiac expression of tumor necrosis factor-alpha (TNF-alpha) plays an important role in the pathogenesis of dilated cardiomyopathy (DCM).
  
  
  OBJECTIVE
  To determine whether CRP co-expresses with TNF-alpha in the myocardium and to examine its association with clinical features in patients with DCM.
  
  
  RESULTS
  Endomyocardial biopsy tissues were obtained from 41 DCM patients and 16 controls by right ventricular endomyocardial biopsy. Levels of CRP and TNF-alpha mRNA were measured by real-time RT-PCR. Immunohistochemistry and in situ hybridization were performed to identify the cellular sources of CRP and TNF-alpha. Both CRP and TNF-alpha mRNA were expressed in myocardium obtained from DCM patients, but not in controls. A positive correlation was found between CRP and TNF-alpha levels. CRP/TNF-alpha double staining was found to be colocalized in the cardiomyocytes of DCM patients. Both forms of mRNA were also expressed in cardiomyocytes. Both CRP and TNF-alpha mRNA levels were negatively correlated with systolic function and positively correlated with left ventricular volume in DCM patients. These mRNA levels were lower in DCM patients treated with a combination of spironolactone and either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) than in patients not treated with these drugs.
  
  
  CONCLUSIONS
  Cardiac expression of CRP with TNF-alpha may function as a proinflammatory mediator in DCM and may be related to the clinical severity of DCM. Expression of both of these proteins was decreased in DCM patients receiving spironolactone and either ACEIs or ARBs.
authors.affiliation: Second Department of Internal Medicine, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan. m_satoh@imu.ncvc.go.jp
authors.forename: Mamoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Tomonari
authors.initials: T
authors.lastname: Akatsu
authors.forename: Yudai
authors.initials: Y
authors.lastname: Shimoda
authors.forename: Ikuo
authors.initials: I
authors.lastname: Segawa
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hiramori
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009206:Myocardium / Q000378:metabolism*; D013148:Spironolactone / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D014409:Tumor Necrosis Factor-alpha; D013148:Spironolactone; D002097:C-Reactive Protein