Contribution of Acquired Factors to the Pathogenesis of Dilated Cardiomyopathy : – The Cause of Dilated Cardiomyopathy: Genetic or Acquired? (Acquired-Side) –
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概要
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Although genetic abnormalities play a pivotal role in the development of dilated cardiomyopathy (DCM), acquired infection and autoimmune abnormalities, or both, appear to be predominant underlying disorders. Of these, viral infection causes target organ damage via perforin produced by suppressor T cells. Thereafter, various antigens released from damaged myocytes are presented on the major histocompatibility complex II, which is expressed in antigen-presenting cells, resulting in activation of both cellular (Th1) and humoral (Th2) immunity. Various antimyocardial antibodies are detected in the serum of patients with DCM and recent findings suggest that at least some of them are directly related to the pathophysiology of DCM. An autoantibody targeting the β1-adrenergic receptor is related to the persistent myocardial damage resulting in DCM and provides the substrate for fatal ventricular arrhythmias. An antibody for the muscarinic M2 receptor is related to atrial fibrillation, an antibody targeting Na-K-ATPase is closely related to sudden cardiac death from fatal ventricular arrhythmias, and an autoantibody for troponin I increases the L-type calcium current and is related to myocardial damage. On the other hand, genetic factors are also involved in susceptibility to viral infection and aberrations of acquired immunity, including antigen presentation and autoantibody production. In conclusion, acquired factors are predominant causes of DCM, although the 2 predisposing factors are also linked to genetic abnormalities. (Circ J 2011; 75: 1766-1773)
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