論文 - 詳細
| RRC ID | 44281 |
|---|---|
| 著者 | 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. |
| タイトル | Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction. |
| ジャーナル | PLoS One |
| 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. |
| 巻・号 | 8(1) |
| ページ | e53133 |
| 公開日 | 2013-1-1 |
| DOI | 10.1371/journal.pone.0053133 |
| PII | PONE-D-11-24929 |
| PMID | 23372656 |
| PMC | PMC3553104 |
| MeSH | Animals Aorta / diagnostic imaging Aorta / metabolism* Aorta / pathology C-Reactive Protein / genetics C-Reactive Protein / metabolism* Connective Tissue Growth Factor / genetics Connective Tissue Growth Factor / metabolism Constriction, Pathologic / genetics Constriction, Pathologic / metabolism* Constriction, Pathologic / pathology Extracellular Signal-Regulated MAP Kinases / genetics Extracellular Signal-Regulated MAP Kinases / metabolism Fibrosis Gene Expression Regulation / drug effects Humans Hydrogen Peroxide / pharmacology Hypertrophy, Left Ventricular / diagnostic imaging Hypertrophy, Left Ventricular / genetics Hypertrophy, Left Ventricular / metabolism* Hypertrophy, Left Ventricular / pathology Interleukin-6 / genetics Interleukin-6 / metabolism Mice Mice, Transgenic Myocardium / metabolism* Myocardium / pathology Myocytes, Cardiac / drug effects Myocytes, Cardiac / metabolism Myocytes, Cardiac / pathology Myofibroblasts / drug effects Myofibroblasts / metabolism Myofibroblasts / pathology NF-kappa B / genetics NF-kappa B / metabolism Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Phosphorylation Signal Transduction / drug effects Ultrasonography Ventricular Dysfunction, Left / diagnostic imaging Ventricular Dysfunction, Left / genetics Ventricular Dysfunction, Left / metabolism* Ventricular Dysfunction, Left / pathology |
| IF | 2.74 |
| 引用数 | 22 |
| WOS 分野 | CARDIAC & CARDIOVASCULAR SYSTEMS |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |