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Rheumatology International

, Volume 30, Issue 12, pp 1621–1625 | Cite as

An animal model of chronic rheumatic valvulitis induced by formalin-killed streptococci

  • Xujing Xie
  • Hanjian Zhou
  • Jianlin Huang
  • Huanlei Huang
  • Zhiying Feng
  • Kaiyong Mei
  • Buyun Yu
  • Zulan Su
  • Jieruo GuEmail author
Original Article

Abstract

Rheumatic heart disease is the most severe complication of rheumatic fever. Till date, very few successful animal models of rheumatic valvular disease have been reported. This study aimed at developing a suitable animal model of chronic rheumatic valvulitis for further investigation and prevention of rheumatic heart disease. Lewis rats were immunized with one administration of formalin-killed and sonicated group A streptococci together with Complete Freund’s Adjuvant every 7 days for three cycles followed by group A streptococci alone till killing. Control rats were administered adjuvants and saline. Rats in group 1 were killed 12 weeks after the initial injection. Rats in group 2 and control group were killed 24 weeks after the initial injection. Results 62.5% (5/8) of rats in group 1 developed myocarditis and 50% (4/8) developed valvulitis. Histological examination of cardiac sections showed only cellular infiltrates. In contrast, 75% (6/8) of rats in group 2 developed rheumatic-like myocarditis and 62.5% (5/8) developed chronic valvulitis. Histological manifestations of the hearts in group 2 animals involved not only acute damage such as cellular infiltrates, Aschoff-like cells, verrucous vegetation, but also chronic lesions such as fibrosis, vascular neogenesis. None of the rats (0/8) in control group presented myocarditis or valvulitis. Lewis rat repeatedly immunized with formalin-killed GAS may be a suitable animal model of chronic rheumatic valvulitis. It may be useful for future investigation of the pathogenesis and possible preventive strategies of human rheumatic heart disease.

Keywords

Group A streptococcus Lewis rat Rheumatic valvulitis Rheumatic heart disease 

Notes

Acknowledgments

We thank Professor Tingchung Wang (University of Rochester Medical Center) for critically reviewing the manuscript.

References

  1. 1.
    Veasy LG, Hill HR (1997) Immunologic and clinical correlations in rheumatic fever and rheumatic heart disease. Pediatr Infect Dis J 16:400–407CrossRefPubMedGoogle Scholar
  2. 2.
    Cunningham MW (2003) Autoimmunity and molecular mimicry in the pathogenesis of post-streptococcal heart disease. Front Biosci 8:s533–s543CrossRefPubMedGoogle Scholar
  3. 3.
    Gorton D, Govan B, Olive C, Ketheesan N (2006) A role for an animal model in determining the immune mechanisms involved in the pathogenesis of rheumatic heart disease. Int Congr Ser 1289:289–292CrossRefGoogle Scholar
  4. 4.
    Huang J, Xie X, Lin Z-F, Luo M-Q, Yu B-Y, Gu J-R (2009) Induction of myocarditis lesions in Lewis rats by formalin-killed cells of group A streptococcus. J Int Med Res 37:175–181PubMedGoogle Scholar
  5. 5.
    Su Z (2008) Pathology. In: Yu B (ed) Rheumatic fever and rheumatic heart disease, 1st edn. Guangdong Science & Technology Press, Guangzhou, Guangdong, pp 36–38Google Scholar
  6. 6.
    Quinn A, Kosanke S, Fischetti VA, Factor SM, Cunningham MW (2001) Induction of autoimmune valvular heart disease by recombinant streptococcal M protein. Infect Immun 69(6):4072–4078CrossRefPubMedGoogle Scholar
  7. 7.
    Galvin JE, Hemric ME, Kosanke SD et al (2002) Induction of myocarditis and valvulitis in Lewis rats by different epitopes of cardiac myosin and its implications in rheumatic carditis. Am J Pathol 160(1):297–306PubMedGoogle Scholar
  8. 8.
    Lymbury RS, Olive C, Powell KA et al (2003) Induction of autoimmune valvulitis in Lewis rats following immunization with peptides from the conserved region of group A streptococcal M protein. J Autoimmun 20:211–217CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Xujing Xie
    • 1
  • Hanjian Zhou
    • 1
  • Jianlin Huang
    • 2
  • Huanlei Huang
    • 3
  • Zhiying Feng
    • 4
  • Kaiyong Mei
    • 5
  • Buyun Yu
    • 2
  • Zulan Su
    • 4
  • Jieruo Gu
    • 2
    Email author
  1. 1.Department of CardiologyThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouPeople’s Republic of China
  2. 2.Department of RheumatologyThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouPeople’s Republic of China
  3. 3.Department of Cardiovascular SurgeryGuangdong General HospitalGuangzhouPeople’s Republic of China
  4. 4.Department of PathologyThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouPeople’s Republic of China
  5. 5.Department of PathologyThe Second Affiliated Hospital of Guangzhou Medical CollegeGuangzhouPeople’s Republic of China

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