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| Status |
Public on Jul 30, 2020 |
| Title |
Angiotensin IV mitigates diabetic cardiomyopathy via downregulating FoxO1-mediated autophagy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Activation of the systemic and myocardial rennin-angiotensin-aldosterone system (RAAS) by hyperglycemia plays a critical role in the development of diabetic cardiomyopathy. To test the hypothesis that AngIV protects against diabetic cardiomyopathy via stimulation of AT4R and inhibition of overactive autophagy, diabetic mice were treated with low-, medium- and high-dose AngIV, AT4R antagonist divalinal, forkhead box protein O1 (FoxO1) inhibitor AS1842856 (AS) or their combinations. In vitro, cardiomyocytes were treated with different concentrations of glucose, low-, medium- and high-dose AngIV, divalinal, FoxO1-overexpression plasmid (FoxO1-OE), AS or their combinations.
The results showed that AngIV treatment dose-dependently attenuated left ventricular dysfunction, remodeling, fibrosis, and myocyte apoptosis in diabetic mice. Besides, autophagy and FoxO1 protein expression enhanced by diabetes were dose-dependently suppressed by AngIV treatment. However, these cardioprotective effects of AngIV were completely abolished by divalinal administration. Bioinformatic analyses revealed that the differentially expressed genes were enriched in autophagy, apoptosis, and FoxO signaling pathways among control, diabetes, and diabetes+high-dose AngIV groups. Similar to AngIV, AS treatment ameliorated diabetic cardiomyopathy in mice. In vitro, AngIV inhibited collagen expression, apoptosis, overactive autophagy flux, and FoxO1 nuclear translocation induced by high glucose in cardiomyocytes. However, these protective effects of AngIV were completely blocked by the use of divalinal or FoxO1-OE, and these detrimental effects were reversed by the additional administration of AS. In summary, AngIV treatment dose-dependently attenuated left ventricular dysfunction and remodeling in a mouse model of diabetic cardiomyopathy, and the mechanism involved stimulation of AT4R, suppression of FoxO1 nuclear translocation and inhibition of FoxO1-mediated overactive autophagy.
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| Overall design |
Myocardial tissues were isolated from mice of negative control, diabetes mellitus, and diabetes mellitus+high-dose angiotensin IV groups; four mice in each group
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| Contributor(s) |
Zhang M, Hao P |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jul 29, 2020 |
| Last update date |
Aug 02, 2020 |
| Contact name |
meng zhang |
| E-mail(s) |
xun8815@126.com
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| Organization name |
Shandong University
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| Street address |
Jinan 250012, Shandong, China
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| City |
jinan |
| ZIP/Postal code |
NO. 107 Wenhuaxi Road |
| Country |
China |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (12)
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| GSM4700335 |
NC-1: myocardial tissues from mice, negative control, rep1 |
| GSM4700336 |
NC-2: myocardial tissues from mice, negative control, rep2 |
| GSM4700337 |
NC-3: myocardial tissues from mice, negative control, rep3 |
| GSM4700338 |
NC-4: myocardial tissues from mice, negative control, rep4 |
| GSM4700339 |
DM-1: myocardial tissues from mice, diabetes mellitus, rep1 |
| GSM4700340 |
DM-2: myocardial tissues from mice, diabetes mellitus, rep2 |
| GSM4700341 |
DM-3: myocardial tissues from mice, diabetes mellitus, rep3 |
| GSM4700342 |
DM-4: myocardial tissues from mice, diabetes mellitus, rep4 |
| GSM4700343 |
AngIV-1: myocardial tissues from mice, diabetes mellitus+high-dose angiotensin IV, rep1 |
| GSM4700344 |
AngIV-2: myocardial tissues from mice, diabetes mellitus+high-dose angiotensin IV, rep2 |
| GSM4700345 |
AngIV-3: myocardial tissues from mice, diabetes mellitus+high-dose angiotensin IV, rep3 |
| GSM4700346 |
AngIV-4: myocardial tissues from mice, diabetes mellitus+high-dose angiotensin IV, rep4 |
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| Relations |
| BioProject |
PRJNA649543 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE155377_RAW.tar |
11.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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