Heart specific up-regulation of genes for B-type and C-type natriuretic peptide receptors in diabetic mice

Eur J Clin Invest. 2006 Feb;36(2):69-75. doi: 10.1111/j.1365-2362.2006.01596.x.

Abstract

Background: Diabetes may cause cardiomyopathy characterized by cardiac fibrosis. Recent studies of genetically modified mice have elucidated a role of the natriuretic peptides (NP), type-A and type-B (ANP and BNP), and their common receptor [natriuretic peptide receptor (NPR), type-A] in development of cardiac fibrosis. The role of NP type-C (CNP) and NPR type-B (NPR-B) in the heart is less well established. In this study we examined if diabetes alters heart expression of the genes encoding the NP and its receptors.

Materials and methods: Cardiac mRNA was quantified by real-time PCR in diabetic streptozotocin (STZ)-treated and ob/ob-mice and nondiabetic control mice.

Results: The ob/ob-mice with type-II diabetes displayed highly significant increases of the cardiac mRNA expression of NPR-B and NPR-C while the expression levels of NPR-A, ANP, BNP, and CNP mRNA were similar in ob/ob-mice and controls. Mice with STZ-induced type-I diabetes also showed an increase of heart NPR-B mRNA expression at 12 weeks, but not at 3, 6 or 9 weeks after STZ-treatment. The ANP and NPR-C mRNA expressions were only altered after 3 weeks, whereas BNP, CNP and NPR-A mRNA expressions were not altered in STZ-treated-mouse hearts at any of the time points.

Conclusions: The results show that diabetes in mice confers increased NPR-B gene expression in the heart, suggesting that increased NPR-B signalling may affect development of diabetic cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / genetics
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Type 1 / genetics
  • Guanylate Cyclase / genetics
  • Heart*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Natriuretic Peptide, Brain / genetics
  • Natriuretic Peptide, C-Type / genetics
  • Natriuretic Peptides / genetics*
  • RNA, Messenger / analysis
  • Receptors, Atrial Natriuretic Factor / genetics
  • Up-Regulation / genetics

Substances

  • Natriuretic Peptides
  • RNA, Messenger
  • Natriuretic Peptide, Brain
  • Natriuretic Peptide, C-Type
  • Atrial Natriuretic Factor
  • Guanylate Cyclase
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor A
  • atrial natriuretic factor receptor B