C-reactive protein overexpression exacerbates pressure overload-induced cardiac remodeling through enhanced inflammatory response

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

Research output: Contribution to journalArticle

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Abstract

Serum C-reactive protein (CRP) elevation predicts the development of heart failure in patients with hypertension. CRP activates macrophages and enhances oxidative stress. We hypothesize that CRP itself has a pathogenic role in the development of pressure overload-induced cardiac remodeling. Transgenic mice with human CRP overexpression (CRPtg) and nontransgenic littermates (CON) were subjected to transverse aortic constriction (TAC/CRPtg and TAC/CON) or sham operation (Sham/CRPtg and Sham/CON). One week after operation, in TAC/CRPtg, myocardial mRNA levels of interleukin (IL)-6, CD68, glutathione peroxidase-3 (GPx3), 47-kDa α-subunit of nicotinamide adenine dinucleotide phosphate oxidase (p47phox), and collagen-I, the number of infiltrating Mac-2-positive macrophages, nuclear localization of phosphorylated NF-κB/p65 (p-p65) in cardiomyocytes, nuclear NF-κB-DNA-binding activity, and reactive oxygen species (ROS) content were increased compared to those in TAC/CON. Cardiac fibrosis was more prominent in TAC/CRPtg compared to TAC/CON. Four weeks after operation, heart and lung weights, cardiomyocyte cross-sectional area, and the extent of cardiac fibrosis were greater in TAC/CON than in Sham/CON, and these differences were further augmented in TAC/CRPtg compared to TAC/CON. Left ventricular (LV) fractional shortening was less and LV end-diastolic pressure was higher in TAC/CRPtg than in TAC/CON. Myocardial mRNA levels of angiotensin type 1 receptor, atrial natriuretic factor, IL-6, GPx3, p47, collagen-I, and transforming growth factor (TGF)-β1, the protein level of TGF-β1, and the numbers of Mac-2-positive macrophages and p-p65-positive cells were higher in TAC/CRPtg than in TAC/CON. In conclusion, CRP itself may have a pathogenic role in the development of pressure overload-induced cardiac remodeling, possibly through enhanced inflammation and oxidative stress.

Original languageEnglish
Pages (from-to)208-215
Number of pages8
JournalHypertension
Volume57
Issue number2
DOIs
Publication statusPublished - 2011 Feb

Fingerprint

C-Reactive Protein
Pressure
Macrophages
Transforming Growth Factors
Glutathione Peroxidase
Cardiac Myocytes
Interleukin-6
Oxidative Stress
Fibrosis
Collagen
Messenger RNA
Angiotensin Type 1 Receptor
Atrial Natriuretic Factor
NADP
Constriction
Transgenic Mice
Blood Proteins
Reactive Oxygen Species
Oxidoreductases
Heart Failure

Keywords

  • C-reactive protein
  • cardiac remodeling
  • inflammation
  • macrophage
  • NF-κB/p65
  • pressure overload

ASJC Scopus subject areas

  • Internal Medicine

Cite this

C-reactive protein overexpression exacerbates pressure overload-induced cardiac remodeling through enhanced inflammatory response. / Nagai, Toshiyuki; Anzai, Toshihisa; Kaneko, Hidehiro; Mano, Yoshinori; Anzai, Atsushi; Maekawa, Yuichiro; Takahashi, Toshiyuki; Meguro, Tomomi; Yoshikawa, Tsutomu; Fukuda, Keiichi.

In: Hypertension, Vol. 57, No. 2, 02.2011, p. 208-215.

Research output: Contribution to journalArticle

Nagai, Toshiyuki ; Anzai, Toshihisa ; Kaneko, Hidehiro ; Mano, Yoshinori ; Anzai, Atsushi ; Maekawa, Yuichiro ; Takahashi, Toshiyuki ; Meguro, Tomomi ; Yoshikawa, Tsutomu ; Fukuda, Keiichi. / C-reactive protein overexpression exacerbates pressure overload-induced cardiac remodeling through enhanced inflammatory response. In: Hypertension. 2011 ; Vol. 57, No. 2. pp. 208-215.
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