A Novel Role of Sympathetic Activity in Regulating Mitral Valve Prolapse

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  • Hu Xiang
    Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine
  • Wang Hao-Zhe
    Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine
  • Liu Jun
    Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine
  • Chen An-Qin
    Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine
  • Ye Xiao-Feng
    Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine
  • Zhao Qiang
    Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine

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Abstract

Background: Increased sympathetic activity, commonly reported in mitral valve prolapse, indicates that the sympathetic nervous system might play an important role in regulating mitral interstitial cells. Hence, the aim of this study is to determine the level and pattern of adrenergic receptors expressed in human mitral valve leaflets and to investigate the effect of norepinephrine on physiologic behaviors of mitral interstitial cells. Methods and Results: Immunohistochemistry displayed significantly increased expressions of β1, β2, and α1 adrenergic receptors in mitral valve prolapse. Norepinephrine was found to activate the phenotype of interstitial cells with increased α-SMA expression (2.26 fold). In synthesis, norepinephrine downregulated levels of mRNA for type I to type III collagen in ratio, but increased the elastin gene transcription and glycosaminoglycan levels in valve interstitial cells greatly. In view of the extracellular matrix remodel, sympathetic effects presented catabolic metabolism displaying significantly increased expressions of total, secretory and active MMP-2 protein (matrix metalloproteinase-2), as well as MMP-9 protein. Diminished MMP inhibitor expression, TIMP2, also could reflect this effect in the norepinephrine medium. Conclusions: A novel role for the sympathetic effect in influencing physiologic behaviors in mitral interstitial cells was identified. It is indicated that sympathetic activity could promote myxomatous degeneration in mitral valve prolapse, propagating the disease severity, which might identify potential therapeutic targets.  (Circ J 2014; 78: 1486–1493)<br>

Journal

  • Circulation Journal

    Circulation Journal 78 (6), 1486-1493, 2014

    The Japanese Circulation Society

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