Restorative Dentistry and Endodontics

The Korean Academy of Conservative Dentistry (대한치과보존학회)
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GENE EXPRESSION OF HUMAN CORONARY ARTERY ENDOTHELIAL CELLS IN RESPONSE TO PORPHYROMONAS ENDODONTALIS INVASION

Porphyromonas endodontalis의 침투에 따른 혈관 내피세포의 유전자 발현

  • Kong, Hee-Joung (Department of Conservative Dentistry, Division of Dentistry, Graduate of Kyung Hee University) ;
  • Choi, Kyoung-Kyu (Department of Conservative Dentistry, Division of Dentistry, Graduate of Kyung Hee University) ;
  • Park, Sang-Hyuk (Department of Conservative Dentistry, Division of Dentistry, Graduate of Kyung Hee University) ;
  • Lee, Jin-Yong (Institute of oral biology, Division of Dentistry, Graduate of Kyung Hee University) ;
  • Choi, Gi-Woon (Department of Conservative Dentistry, Division of Dentistry, Graduate of Kyung Hee University)
  • 공희정 (경희대학교 대학원 치의학과 치과보존학교실) ;
  • 최경규 (경희대학교 대학원 치의학과 치과보존학교실) ;
  • 박상혁 (경희대학교 대학원 치의학과 치과보존학교실) ;
  • 이진용 (경희대학교 대학원 치의학과 구강생물학연구소) ;
  • 최기운 (경희대학교 대학원 치의학과 치과보존학교실)
  • Published : 2009.11.30
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Abstract

During the last two decades, there has been an increasing interest in the impact of oral health on atherosclerosis and subsequent cardiovascular disease (CVD). To date, some periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) have been reported to be relevant to CVD. Porphyromonas endodontalis (P. endodontalis), which shares approximately 87% sequence homology with P. gingivalis, is mostly found within infected root canals. However, recent studies reveal that this pathogen also resides in the dental plaque or periodontal pocket in patients with periodontitis. It has been shown that P. endodontalis invades human coronary artery endothelial cells (HCAEC) and coronary artery smooth muscle cells (CASMC). To evaluate whether P. endodontalis can participate in the progression of atherosclerosis and CVD, we examined the changes in transcriptional gene expression profiles of HCAEC responding to invaion by P. endodontalis in this study. The following results were obtained. 1. Porphyromonas endodontalis was invasive of HCAEC. 2. According to the microarray analysis, there were 625 genes upregulated more than two-folds, while there were 154 genes downregulated by half. 3. Upregulated genes were relevant to inflammatory cytokines, apoptosis, coagulation and immune response. Enhanced expression of MMP-1 was also noticeable. 4. The transcription profiles of the 10 selected genes examined by real-time PCR agreed well with those observed in the microarray analysis. Thus, these results show that P. endodontalis presents the potential to trigger and augment atherosclerosis leading to CVD.

본 연구에서는 Porphyromonas endodontalis와 죽상경화증 및 심혈관질환과의 관계를 알아보기 위해, P. endodontalis가 사람의 관상동맥 내피세포에 침투했을 때 나타나는 유전자 발현의 변화를 microarray와 real-time PCR로 측정하였고, 발현이 증가된 유전자 중에서 죽상경화증과 연관된 유전자들이 관련 KEGG pathway 상에서 유의성 있는 영향을 미치는지를 분석하여 다음과 같은 결과를 얻었다. 1. Porphyromonas endodontalis는 사람의 관상동맥 내피세포에 침투하였다. 2. Microarray 분석결과, 대조군보다 발현이 2배 이상 증가된 유전자는 625개였고, 1/2이하로 감소된 유전자는 154개였다. 3. 발현이 2배 이상 증가된 유전자 중에는 염증성 cytokine 및 chemokine, 세포자멸사, 혈액응고와 면역반응 관련 유전자들이 포함되었다. 4. Microarray 분석결과를 확인하기 위해 발현이 2배 이상 증가된 유전자 중에서 10개의 유전자를 선택하여 real-time PCR을 시행하였고, 그 결과 microarray에서와 마찬가지로 발현 정도가 대조군보다 모두 높게 나타났다. 따라서 P. endodontalis가 사람의 관상동맥 내피세포에 만성적으로 작용했을 때, 심혈관질환에서 중요한 부분을 차지하는 죽상경화증을 유발하는 위험 요소 중의 하나로 작용할 수 있을 것으로 판단된다. 이와 관련된 자세한 기전을 이해하기 위해서는 앞으로 더 많은 연구가 필요할 것으로 보인다.

Keywords

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