CCN2 protein is an announcing marker for cardiac remodeling following STZ-induced moderate hyperglycemia in mice.
Diabetes causes changes in the myocardium, which are often called diabetic cardiomyopathy. This condition has been extensively investigated in animal models with high glucose levels. Nevertheless, it has not been investigated whether moderate hyperglycemia, in the absence of other features of metabolic syndrome, may also cause similar changes in the heart. The aim of the study was to assess changes in the myocardium in an animal model of mild type 1 diabetes. Moderate hyperglycemia was induced in 8- to 10-week-old male C57BL6J mice by 5 intraperitoneal injections of streptozotocin (40 mg/kg). After 16 weeks, they were sacrificed, and left ventricle (LV) dimensions and extent of cardiac fibrosis were assessed by morphometry. The abundance of CCN proteins in LVsamples was assessed using western blotting, while activity of metalloproteinase 2 was established in zymography. Real time PCR was used to investigate the expression of transforming growth factor beta1 (TGFbeta1) and atrial natriuretic peptide. Mice with moderate hyperglycemia presented comparable cardiac dimensions with fibrosis and hypertrophy parameters as the non-diabetic controls. However, the abundance of profibrotic CCN2 protein was significantly increased in hyperglycemic animals (1.67 +/- 0.28 vs. 1 +/- 0.47, p < 0.05). Interestingly, this change was independent from the TGFbeta1 expression, as its RNA abundance was similar in both groups. Moderate hyperglycemia also caused an increase in the activity of the metalloproteinase 2 (1.21 +/- 0.17 vs. 1 +/- 0.07, p < 0.05). Despite diabetes, no profound changes in cardiac morphology were found. In our animal model, moderate hyperglycemia caused activation of a profibrotic gene expression program, which was counterbalanced by the increase of metalloproteinase activity.
Kamiński
Karol A
KA
Department of Cardiology, Medical University of Białystok, M. Curie-Skłodowskiej 24A, PL 15-276 Białystok, Poland.
Szepietowska
Barbara
B
Bonda
Tomasz
T
Kozuch
Marcin
M
Mencel
Joanna
J
Małkowski
Andrzej
A
Sobolewski
Krzysztof
K
Kovalchuk
Oksana
O
Chyczewski
Lech
L
Szelachowska
Małgorzata
M
Górska
Maria
M
Musiał
Włodzimierz J
WJ
Winnicka
Maria M
MM
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D055511:CCN Intercellular Signaling Proteins / Q000378:metabolism; D009202:Cardiomyopathies / Q000175:diagnosis* / Q000473:pathology*; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020257:Ventricular Remodeling
D015415:Biomarkers; D055511:CCN Intercellular Signaling Proteins; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D009320:Atrial Natriuretic Factor; D020778:Matrix Metalloproteinase 2