Basic research

Periodontitis aggravates transverse aortic constriction-induced cardiac hypertrophy in mice

  • Lu LI ,
  • Yulin LI ,
  • Yan LIU ,
  • Shengzhong DUAN
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  • Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200125, China
DUAN Shengzhong, E-mail: duansz@shsmu.edu.cn.

Received date: 2022-05-18

  Accepted date: 2022-08-06

  Online published: 2022-09-28

Supported by

National Natural Science Foundation of China(81725003);Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20212500)

Abstract

Objective ·To study the effects of periodontitis (PD) on transverse aortic constriction (TAC)-induced cardiac hypertrophy in mice and explore the mechanisms. Methods ·Twenty-five C57BL/6J mice were randomly divided into Sham operation (Sham) group, transverse aortic constriction (TAC) group, and periodontitis combined with TAC (TAC+PD) group. PD was induced by ligation of mouse molars and application of subgingival plaques of PD patients. TAC surgery was performed after the establishment of PD model. Cardiac function was assessed by echocardiography at 4 weeks after Sham or TAC surgery. The mice were then sacrificed and the samples were collected for quantitative realtime PCR (qRT-PCR), immunohistochemistry, immunofluorescence, and 16S rRNA gene sequencing. Results ·The mice in the TAC+PD group manifested significantly more resorption of the alveolar bone and higher expression of inflammatory genes in gingiva compared to Sham and TAC groups, demonstrating successful establishment of PD models in TAC mice. Compared to those in the TAC group, the mice in the TAC+PD group had significantly lower left ventricular ejection fraction (EF) and left ventricular shortening fraction (FS), illustrating that PD exacerbated TAC-induced cardiac dysfunction. Compared to those in the TAC group, the mice in the TAC+PD group had significantly bigger heart weight to body weight ratio (HW/BW) and heart weight to tibia length ratio (HW/TL), lung weight to body weight ratio (LW/BW), and cross-sectional area of cardiomyocytes, as well as higher expression of hypertrophy-related genes, demonstrating that PD exacerbated TAC-induced cardiac hypertrophy and heart failure. Compared to those in the TAC group, the mice in the TAC+PD group had significantly larger fibrotic areas and higher expression of fibrosis-related genes in the heart, bigger spleen weight to tibia length ratio (SW/TL) and higher expression of inflammatory genes in the heart, illustrating that PD exacerbated TAC-induced cardiac fibrosis and inflammation. Results of 16S rRNA gene sequencing showed that relative abundances of Streptococcus and Veillonella were significantly increased in the oral ligatures of mice in the TAC+PD group compared to the TAC group. Relative abundances of Ralstonia, and Pelomonas were significantly increased in the hearts of mice in the TAC+PD group. Comparison of oral microbiota and heart microbiota of the mice in the TAC+PD group revealed that relative abundances of Ralstonia and Pelomonas in hearts were significantly higher than those in oral ligatures. Conclusion ·PD aggravates TAC-induced cardiac dysfunction, cardiac hypertrophy, fibrosis, and inflammation in mice. The mechanisms may be related to alterations in oral microbiota, particularly bacterial genera including Ralstonia and Pelomonas.

Cite this article

Lu LI , Yulin LI , Yan LIU , Shengzhong DUAN . Periodontitis aggravates transverse aortic constriction-induced cardiac hypertrophy in mice[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022 , 42(9) : 1275 -1287 . DOI: 10.3969/j.issn.1674-8115.2022.09.014

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