HSP75 protects against cardiac hypertrophy and fibrosis

J Cell Biochem. 2011 Jul;112(7):1787-94. doi: 10.1002/jcb.23091.


Cardiac hypertrophy, a major determinant of heart failure, is associated with heat shock proteins (HSPs). HSP75 has been reported to protect against environmental stresses; however, its roles in cardiac hypertrophy remain unclear. Here, we generated cardiac-specific inducible HSP75 transgenic mice (TG) and cardiac hypertrophy was developed at 4 weeks after aortic banding in TG mice and wild-type littermates. The results revealed that overexpression of HSP75 prevented cardiac hypertrophy and fibrosis as assessed by heart weight/body weight ratio, heart weight/tibia length ratio, echocardiographic and hemodynamic parameters, cardiomyocyte width, left ventricular collagen volume, and gene expression of hypertrophic markers. Further studies showed that overexpression of HSP75 inhibited the activation of TAK/P38, JNK, and AKT signaling pathways. Thus, HSP75 likely reduces the hypertrophy and fibrosis induced by pressure overload through blocking TAK/P38, JNK, and AKT signaling pathways.

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / genetics
  • Atrial Natriuretic Factor / metabolism
  • Body Weight
  • Cardiomegaly / genetics*
  • Cardiomegaly / metabolism
  • Cardiomegaly / pathology
  • Cell Size
  • Collagen / metabolism
  • Fibrosis
  • HSP90 Heat-Shock Proteins / genetics*
  • HSP90 Heat-Shock Proteins / metabolism
  • Heart Ventricles / metabolism
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle Cells / metabolism
  • Muscle Cells / pathology
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism
  • Organ Size
  • Phosphorylation
  • Recombinant Proteins / genetics*
  • Recombinant Proteins / metabolism
  • Transcription, Genetic
  • Ventricular Pressure
  • Ventricular Remodeling


  • HSP90 Heat-Shock Proteins
  • Recombinant Proteins
  • TRAP1 protein, human
  • Atrial Natriuretic Factor
  • Collagen
  • Myosin Heavy Chains