Long Pentraxin PTX3 Exacerbates Pressure Overload-Induced Left Ventricular Dysfunction

Satoshi Suzuki, Tetsuro Shishido, Akira Funayama, Shunsuke Netsu, Mitsunori Ishino, Tatsuro Kitahara, Toshiki Sasaki, Shigehiko Katoh, Yoichiro Otaki, Tetsu Watanabe, Yoko Shibata, Alberto Mantovani, Yasuchika Takeishi, Isao Kubota

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Abstract

Background: Left ventricular hypertrophy is enhanced by an inflammatory state and stimulation of various cytokines. Pentraxin 3 (PTX3) is rapidly produced in response to inflammatory signals, and high plasma PTX3 levels are seen in patients with heart failure. This study aimed to examine the influence of PTX3 on cardiac hypertrophy and left ventricular dysfunction with respect to pressure overload. Methods and Results: PTX3 systemic knockout (PTX3-KO) mice, transgenic mice with cardiac-specific overexpression of PTX3 (PTX3-TG), and the respective wild-type (WT) littermate mice were subjected to transverse aortic constriction (TAC) or a sham operation. Cardiac PTX3 expression increased after TAC in WT mice. In vitro, hydrogen peroxide induced the expression of PTX3 in both cardiac myocytes and cardiac fibroblasts. Recombinant PTX3 phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) in cardiac fibroblasts. Phosphorylation of cardiac ERK1/2 and nuclear factor kappa-B after TAC was attenuated in the PTX3-KO mice but was enhanced in the PTX3-TG mice compared with WT mice. Interleukin-6 and connective tissue growth factor production was lower in the PTX3-KO mice than in the WT mice, but this was augmented in the PTX3-TG mice than in the WT mice. Echocardiography revealed that adverse remodeling with left ventricular dysfunction, as well as with increased interstitial fibrosis, was enhanced in PTX3-TG mice, while these responses were suppressed in PTX3-KO mice. Conclusion: The local inflammatory mediator PTX3 directly modulates the hypertrophic response and ventricular dysfunction following an increased afterload.

Original languageEnglish
Article numbere53133
JournalPLoS One
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 29 2013

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Suzuki, S., Shishido, T., Funayama, A., Netsu, S., Ishino, M., Kitahara, T., Sasaki, T., Katoh, S., Otaki, Y., Watanabe, T., Shibata, Y., Mantovani, A., Takeishi, Y., & Kubota, I. (2013). Long Pentraxin PTX3 Exacerbates Pressure Overload-Induced Left Ventricular Dysfunction. PLoS One, 8(1), [e53133]. https://doi.org/10.1371/journal.pone.0053133