Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
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Upregulation of Connexin43 Expression in Mitral Valves in a Rabbit Model of Hypercholesterolemia

고콜레스테롤혈증을 유발한 토끼의 승모판막에서 Connexin43 발현의 증가

  • Kwon, Jong-Bum (Department of Thoracic and Cardiovascular Surgery, Daejeon St. Mary’s Hospital, The Catholic University of Korea) ;
  • Park, Chan-Beom (Department of Thoracic and Cardiovascular Surgery, St. Paul's Hospital, The Catholic University of Korea) ;
  • Sa, Young-Jo (Department of Thoracic and Cardiovascular Surgery, St. Mary’s Hospital, The Catholic University of Korea) ;
  • Kim, Young-Du (Department of Thoracic and Cardiovascular Surgery, Bucheon St. Mary’s Hospital, The Catholic University of Korea) ;
  • Moon, Seok-Whan (Department of Thoracic and Cardiovascular Surgery, St. Paul's Hospital, The Catholic University of Korea) ;
  • Kim, Chi-Kyung (Department of Thoracic and Cardiovascular Surgery, St. Paul's Hospital, The Catholic University of Korea)
  • 권종범 (가톨릭대학교 대전성모병원 흉부외과) ;
  • 박찬범 (가톨릭대학교 성바오로병원 흉부외과) ;
  • 사영조 (가톨릭대학교 성모병원 흉부외과) ;
  • 김영두 (가톨릭대학교 부천성모병원 흉부외과) ;
  • 문석환 (가톨릭대학교 성바오로병원 흉부외과) ;
  • 김치경 (가톨릭대학교 성바오로병원 흉부외과)
  • Received : 2010.01.22
  • Accepted : 2010.02.16
  • Published : 2010.08.05
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Abstract

Background: Connexin 43-mediated gap junctional communication plays an important role in atherosclerosis. Numerous studies have demonstrated a correlation between mitral valve annular calcification and atherosclerotic disease. However, the relevance of connexin 43 to mitral valve disease remains unclear. We hypothesized that the mechanism contributing to mitral valve disease is associated with alterations in cell-to-cell communication mediated by changes in Connexin 43 expression. Material and Method: Twenty male New Zealand rabbits were divided into two groups: animals in group 1 (n=10) were fed a normal chow diet, whilst those in group 2 (n=10) received a diet containing 1% cholesterol for 12 weeks. After sacrificing the animals, the mitral valves were excised and analyzed with immunohistochemical staining and Real-time Reverse Transcriptase polymerase chain reaction (real time RT-PCR). Result: Myofibroblasts and macrophages were found concentrated within the endothelial layer on the ventricular side of the leaflet in the cholesterol diet group. Immunohistochemial staining showed elevated expression of connexin43 in the cholesterol diet group. Real-time RT-PCR revealed increased connexin43 mRNA levels in mitral valves from hypercholesterolemic animals. Conclusion: Our finding that connexin43 expression is increased in mitral valves of hypercholesterolemic rabbits suggests that alterations in cell-to-cell communication via connexin43 containing gap junctions play a role in the development of mitral valve disease in hypercholesterolemia.

배경: 승모판막의 석회화는 죽상경화와 밀접한 연관관계가 있는 것으로 알려져 있다. 그러나, 승모판막 질환에서 혈관 죽상경화에 중요한 역할을 하는 것으로 알려진 Connexin43 매개에 의한 Gap junction의 신호전달의 변화는 잘 알려져 있지 않다. 따라서, 저자들은 승모판막의 퇴행성 변화과정이 Gap junction을 통한 세포간 신호전달의 변화와 연관이 있을 것이라고 가정하였다. 대상 및 방법: 뉴질랜드산 토끼 20마리를 2군으로 나눈후, 1군(10마리)에서는 정상식이를 시행하였고, 2군(10마리)에서는 1% 콜레스테롤식이를 12주간 시행하였다. 각군의 토끼들의 혈장에서 총 콜레스테롤, 중성지방, 저밀도 콜레스테롤, 고밀도 콜레스테롤 수치를 측정하였으며, 승모판막을 절제하여 Connexin43, 근육섬유모세포 그리고 대식세포에 대한 면역조직화학염색을 시행하였으며, Connexin43에 대한 정량적 검사를 위하여 Real-time Reverse Transcriptase polymerase chain reaction (real time RT-PCR)을 시행하였다. 결과: 면역조직화학염색에서 근육섬유모세포와 대식세포의 발현은 콜레스테롤 식이를 시행한 군의 승모판막에서 증가되었으며, Connexin43의 발현도 콜레스테롤 식이군에서 증가되어 있었다. RT-PCR을 이용한 정량적 검사에서 Connexin43의 발현은 콜레스테롤 식이군에서 의미있게 증가되어 있었다(p<0.01). 결론: 고콜레스테롤혈증이 유발된 토끼의 승모판막의 변화는 초기 죽상경화와 유사한 과정을 보이며, Connex43의 발현이 증가되었다. 따라서 고콜레스테롤혈증에서의 승모판막질환은 증가된 Connexin43매개 Gap junction을 통한 세포간 신호전달의 변화가 중요한 역할을 한다고 생각된다.

Keywords

References

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