title: Overexpression of human C-reactive protein exacerbates left ventricular remodeling in diabetic cardiomyopathy.
abstract: BACKGROUND
  C-reactive protein (CRP) is known to be a pathogenic agent in the cardiovascular system. However, the effect of CRP on heart failure has not been elucidated. The effect of human CRP on cardiac dysfunction induced by diabetes mellitus (DM) using human CRP-overexpressing transgenic mice (CRP-Tg) was examined.
  
  
  RESULTS
  DM was induced in male wild-type mice (Wt/DM) and CRP-Tg (CRP/DM) by an injection of streptozotocin. Non-diabetic wild-type mice (Wt/Con) and CRP-Tg (CRP/Con) served as controls. Echocardiography and hemodynamic measurements 6 weeks after injection showed lower fractional shortening and left ventricular (LV) dP/dt max in CRP/DM compared with Wt/DM. Myocardial mRNA levels of interleukin-6, tumor necrosis factor-α, plasminogen activator inhibitor-1, angiotensin type 1 receptor, angiotensinogen, NADPH oxidase subunits (p47(phox), gp91(phox)), glutathione peroxidase-3. and connective tissue growth factor were increased in CRP/DM compared with Wt/DM. Nuclear staining of 8-hydroxydeoxyguanosine was also increased in CRP/DM compared with Wt/DM. CRP/DM was associated with increased terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling positive cells and a higher ratio of Bax/Bcl-2 proteins compared with Wt/DM. The extent of cardiac fibrosis assessed by Sirius red staining and immunohistochemical staining for collagen type 1 was significantly increased in CRP/DM compared with Wt/DM.
  
  
  CONCLUSIONS
  Overexpression of human CRP exacerbates LV dysfunction and remodeling in diabetic cardiomyopathy, possibly through enhancement of the inflammation, renin-angiotensin system, and oxidative stress.
authors.affiliation: Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Mano
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Anzai
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kaneko
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagatomo
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nagai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Anzai
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Meguro
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology; D013311:Streptozocin / Q000009:adverse effects; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D016207:Cytokines; D013311:Streptozocin; D002097:C-Reactive Protein