Selective decrease of components of the creatine kinase system and ATP synthase complex in chronic Chagas disease

Priscila Camillo Teixeira1, Ronaldo Honorato Barros Santos, Alfredo Inácio Fiorelli

  • 1Laboratory of Immunology, Heart Institute, School of Medicine, University of São Paulo, São Paulo, Brazil.

Insights

Chronic Chagas disease cardiomyopathy (CCC) shows reduced levels of key enzymes for ATP production, indicating a more severe energy deficit compared to other cardiomyopathies. This impairment may explain the loss of contractile function in CCC patients.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory condition with a poor prognosis.
  • Heart failure in CCC is linked to impaired myocardial energy metabolism and contractile dysfunction.
  • Trypanosoma cruzi infection causes CCC, prevalent in Latin America.

Purpose of the Study:

  • To investigate myocardial gene and protein expression of key ATP-producing mitochondrial enzymes.
  • To assess enzyme activity in end-stage CCC, idiopathic dilated cardiomyopathy (IDC), and ischemic cardiomyopathy (IC).
  • To correlate metabolic changes with contractile dysfunction in CCC.

Main Methods:

  • Analysis of myocardial samples from CCC, IC, IDC patients, and heart donors.
  • Quantification of mitochondrial creatine kinase (CKMit), muscular creatine kinase (CKM), and ATP synthase subunits (alpha, beta) using immunoblotting and real-time RT-PCR.
  • Assessment of total myocardial creatine kinase (CK) activity.

Main Results:

  • CKM protein levels and CK activity were reduced across all cardiomyopathy groups.
  • ATP synthase alpha chain protein levels and total CK activity were significantly lower in CCC compared to IC and IDC.
  • CCC myocardium exhibited a selective reduction in enzymes vital for cytoplasmic ATP maintenance.

Conclusions:

  • Selective impairment of the creatine kinase (CK) system in CCC may contribute to reduced inotropic reserve.
  • Lower ATP synthase alpha levels suggest decreased ATP generation via oxidative phosphorylation in CCC.
  • CCC patients exhibit a more pronounced myocardial energetic deficit than other dilated cardiomyopathies.
Abstract

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