Figure 9

Expression patterns of cardioprotective Agtr2 and Med13, and cardio-deleterious miR-208a and diabetic marker miR-29 family miRNAs in heart tissues of 5-month old healthy and diabetic, male and female rats. (a) Graph shows qRT-PCR data on the expression of cardiac Agtr2 (AT2R) mRNA. ZL-F rats had a significantly higher expression of Agtr2 mRNA compared to ZL-M rats, indicating a sex difference in the expression of cardiac AT2R. Agtr2 mRNA expression was strongly suppressed in ZDF-F rats compared to ZL-F rats, indicating that diabetes progression leads to loss of cardioprotective AT2R expression in females. There was no significant loss of Agtr2 mRNA expression in ZDF-M rats. (b) Graph shows qRT-PCR data on cardiac expression of Med13. ZL-F had a significantly greater expression of Med13 mRNA than ZL-M, suggesting a sex bias. Cardiac Med13 expression was suppressed in both ZDF-F and ZDF-M compared to lean controls, indicating a diabetes-associated suppression of Med13. (c) Graphs show qRT-PCR data on the expression of cardiac miR-208a. Cardiac miR-208a expression was elevated in both ZDF-F and ZDF-M compared to lean controls, indicating a diabetes-associated elevation of cardiac miR-208a. The miR-208a expression was higher in both ZL-F and ZDF-F compared to their male counterparts. Thus miR-208a exhibits sex bias. Interestingly, ZL-F had higher cardiac Med13 expression than ZL-M. (d–f) Graphs show qRT-PCR data on the expression of cardiac microRNA miR-29a, b and c. Expression of all miR-29 family miRNAs were increased in ZDF-F and ZDF-M. miR-29c was the most differentially expressed miRNA between male rats (f) whereas miR-29b was the most differentially expressed miRNA between female rats (e). Additionally, miR-29b levels were higher in ZDF-F rats compared to ZDF-M rats. Thus, there were sex differences in miR-29 family miRNA expression. Number of animals per group ranged from 6–8 for ZL-M and 4–6 for all other groups. Values are means ± SEM. p-values are noted and were determined by two-way ANOVAS, sex; D, diabetes; INT, interaction. *p < 0.05 vs. ZL-F; † p < 0.05 vs. ZL-M; # p < 0.05 vs. ZDF-F.