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


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.
Christoffersen
C
C
Department of Biochemistry, Rigshospitalet, University of Copenhagen, Denmark.
Bartels
E D
ED
Nielsen
L B
LB
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D006162:Guanylate Cyclase / Q000235:genetics; D006321:Heart; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D020098:Natriuretic Peptide, C-Type / Q000235:genetics; D045265:Natriuretic Peptides / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D000099242:Atrial Natriuretic Factor Receptor B
D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D045265:Natriuretic Peptides; D012333:RNA, Messenger; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B; C091715:atrial natriuretic factor receptor A