Overexpression of human C-reactive protein exacerbatesleft ventricular remodeling in diabetic cardiomyopathy

Yoshinori Mano, Toshihisa Anzai, Hidehiro Kaneko, Yuji Nagatomo, Toshiyuki Nagai, Atsushi Anzai, Yuichiro Maekawa, Toshiyuki Takahashi, Tomomi Meguro, Tsutomu Yoshikawa, Keiichi Fukuda

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

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 dysfunctioninduced by diabetes mellitus (DM) using human CRP-overexpressing transgenic mice (CRP-Tg) wasexamined.Methods and Results: DM was induced in male wild-type mice (Wt/DM) and CRP-Tg (CRP/DM) by an injectionof streptozotocin. Non-diabetic wild-type mice (Wt/Con) and CRP-Tg (CRP/Con) served as controls. Echocardiographyand hemodynamic measurements 6 weeks after injection showed lower fractional shortening and leftventricular (LV) dP/dt max in CRP/DM compared with Wt/DM. Myocardial mRNA levels of interleukin-6, tumornecrosis factor-α, plasminogen activator inhibitor-1, angiotensin type 1 receptor, angiotensinogen, NADPH oxidasesubunits (p47 phox, gp91 phox), glutathione peroxidase-3. and connective tissue growth factor were increased inCRP/DM compared with Wt/DM. Nuclear staining of 8-hydroxydeoxyguanosine was also increased in CRP/DMcompared with Wt/DM. CRP/DM was associated with increased terminal deoxynucleotidyl transferase-mediateddUTP nick end-labeling positive cells and a higher ratio of Bax/Bcl-2 proteins compared with Wt/DM. The extentof cardiac fibrosis assessed by Sirius red staining and immunohistochemical staining for collagen type 1 was significantlyincreased 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.

Original languageEnglish
Pages (from-to)1717-1727
Number of pages11
JournalCirculation Journal
Volume75
Issue number7
DOIs
Publication statusPublished - 2011 Jul

Keywords

  • C-reactive protein
  • Diabetes mellitus
  • Heart failure
  • Inflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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